High convection home hemodialysis/hemofiltration and sorbent system

ABSTRACT

A system, method and apparatus for performing a renal replacement therapy is provided. In one embodiment, two small high flux dialyzers are connected in series. A restriction is placed between the two dialyzers in the dialysate flow path. The restriction is variable and adjustable in one preferred embodiment. The restriction builds a positive pressure in the venous dialyzer, causing a high degree of intentional backfiltration. That backfiltration causes a significant flow of dialysate through the high flux venous membrane directly into the patient&#39;s blood. That backfiltered solution is subsequently ultrafiltered from the patient from the arterial dialyzer. The diffusion of dialysate into the venous filter and removal of dialysate from the arterial dialyzer causes a convective transport of toxins from the patient. Additionally, the dialysate that does not diffuse directly into the patient but instead flows across the membranes of both dialyzers provides a diffusive clearance of waste products.

PRIORITY CLAIM

This application claims the benefit of U.S. Provisional PatentApplication No. 60/517,730, filed Nov. 5, 2003, entitled “HighConvection Home Hemodialysis/Hemofiltration And Sorbent System”, theentire contents of which are hereby incorporated by reference and reliedupon.

BACKGROUND OF THE INVENTION

The present invention relates generally to medical treatments. Morespecifically, the present invention relates to medical fluid treatments,such as the treatment of renal failure and fluid removal for congestiveheart failure.

Hemodialysis (“HD”) in general uses diffusion to remove waste productsfrom a patient's blood. A diffusive gradient that occurs across thesemi-permeable dialyzer between the blood and an electrolyte solutioncalled dialysate causes diffusion. Hemofiltration (“HF”) is analternative renal replacement therapy that relies on a convectivetransport of toxins from the patient's blood. This therapy isaccomplished by adding substitution or replacement fluid to theextracorporeal circuit during treatment (typically ten to ninety litersof such fluid). That substitution fluid and the fluid accumulated by thepatient in between treatments is ultrafiltered over the course of the HFtreatment, providing a convective transport mechanism that isparticularly beneficial in removing middle and large molecules (inhemodialysis there is a small amount of waste removed along with thefluid gained between dialysis sessions, however, the solute drag fromthe removal of that ultrafiltrate is not enough to provide convectiveclearance).

Hemodiafiltration (“HDF”) is a treatment modality that combinesconvective and diffusive clearances. HDF uses dialysate to flow througha dialyzer, similar to standard hemodialysis, providing diffusiveclearance. In addition, substitution solution is provided directly tothe extracorporeal circuit, providing convective clearance.

Home hemodialysis (“HHD”) has declined in the last twenty years eventhough the clinical outcomes of this modality are more attractive thanconventional hemodialysis. One of the drawbacks of home hemodialysis isthe need for a dedicated water treatment, which includes equipment,water connection and drainage. Installing and using those components isa difficult and cumbersome task that can require a patient's home to bemodified. Nevertheless, there are benefits to daily hemodialysistreatments versus bi- or tri-weekly visits to a treatment center. Inparticular, a patient receiving more frequent treatments removes moretoxins and waste products than a patient receiving less frequent butperhaps longer treatments.

SUMMARY OF THE INVENTION

The present invention provides a system, method and apparatus thatperforms a daily renal replacement therapy, which combines bothdiffusion and convection transport from the patient. In hemodialysis,high flux membranes can in some cases backfilter fluid from thedialysate to the blood even though, on balance, net fluid flow is fromthe patient. That backfiltration is due to a pressure differentialbetween the inlet/outlet of the blood and inlet/outlet of dialysate inspecific areas of the dialyzer. The present invention capitalizes onthat phenomenon.

In one embodiment, two small high flux dialyzers are connected fluidlyto the cassette in series. Dialysate and blood flow in a countercurrentmanner through the dialyzers and extracorporeal circuit. In oneembodiment, however, the dialysate flow through the dialyzers canalternatively be co-current or in the same direction as the flow ofblood through the blood circuit. A restriction is placed between the twodialyzers in the dialysate flow path. The restriction is variable andadjustable in one preferred embodiment to account for differenttreatment conditions or to be adjusted during a single treatment. Therestriction is alternatively a simple fixed restriction, such as anorifice plate with a smaller orifice. Due to the restriction between thefilters, a positive pressure is built in the venous dialyzer, causing ahigh degree of intentional backfiltration. Depending on the size of therestriction between the dialyzers, that backfiltration causes asignificant flow of dialysate through the high flux venous membranedirectly into the blood. That backfiltered solution is subsequentlyultrafiltered from the patient from the arterial dialyzer. The movementof dialysate into the blood in the venous filter and removal ofdialysate from the arterial dialyzer causes a convective transport oftoxins from the patient. Additionally, the dialysate that does not movedirectly into the patient but instead flows across the membranes of bothdialyzers provides a diffusive clearance of waste products.

The system therefore acts as a hemodiafiltration system providing bothconvective and diffusive clearances. The system in one embodiment isconfigured for home use, wherein at least a portion of the dialysate andextracorporeal flow paths is sterilized and provided in a disposablecassette, which is loaded into a home pumping apparatus. For example,the system can be a portable device that uses an integrated disposablefluid management system or cassette and a sterile, prepackaged solutionto perform a hemodialysis therapy. The system in one embodiment isparticularly suited for home use because of its compact size, ease oftherapy setup, and lack of need for a water treatment and dialysateproportioning system.

Unlike current hemodialysis machines, the patient does not have tomanage complicated tubing sets. The patient simply places the cassetteinto the renal failure therapy machine, connects solution bags to themachine and starts an automated priming sequence. When the priming iscomplete, the patient connects the bloodlines to the patient's body andstarts the dialysis therapy. At the end of treatment the patient's bloodis returned to the patient's body. The patient merely discards theultrafiltrate (“UF”) waste and the therapy ends without the patienthaving to perform a complicated disinfection procedure.

In one embodiment, the cassette-based system operates as follows. Ablood pump pulls blood from the patient, pushes it through bothhemodialyzers and returns the blood to the patient. Dialysate solutionis drawn from a dialysate source and heated to a desired patienttemperature. Infusion pumps pump fresh dialysate from the bag into thevenous dialyzer. The restriction is placed in the dialysate flow pathbetween the two dialyzers to facilitate the backfiltration of dialysateinto the bloodline via venous dialyzer. The restriction is preferablyvariable but alternatively fixed.

The flow out of the infusion pumps pushes fluid at the restrictioncreating a positive pressure in the venous hemodialyzer. Using a highflux membrane, the backpressure forces a portion of the dialysate, e.g.,fifty percent or more, into the patient's bloodline. The rest of thedialysate flows through to the arterial dialyzer. Drain pumps removefrom the flow paths an equivalent amount of fluid as delivered by theinfusion pumps as well as any fluid loss that the patient has gained inthe interdialytic period. The spent fluid and ultrafiltrate are then putinto a drain bag or dumped to an external drain.

The cassette-based dialysate pumps are controlled to balance thedialysate flow to the venous dialyzer with the dialysate flow from thearterial dialyzer so that the patient fluid status is maintained. Due tothat balancing capability an identical amount of fluid is ultrafilteredfrom the patient in the arterial hemodialyzer as is backfiltered intothe extracorporeal circuit in the venous dialyzer. Ultrafiltering thisfluid from the blood creates a solute drag effect providing a convectivetransport of toxins similar to hemofiltration. Since some dialysateflows along the fiber in the venous to arterial dialyzer there is alsodiffusive transport of toxins from the blood.

Air bubble detectors, heating elements, pressure sensors, temperaturesensors, etc., are also integrated into the cassette for both thedialysate management and extracorporeal blood sides as necessary toallow for a safe treatment for the patient and reliable operation of thesystem.

Recently published studies show that ultrapure dialysate produces betteroutcomes when compared to standard dialysate. The prepackaged,sterilized dialysate used in one embodiment of the present invention mayproduce outcomes that are as good as, if not better than, ultrapuredialysate. It should be appreciated however that the present inventionis not limited to the use of prepackaged dialysate bags, but instead,may use dialysate prepared on-line or at home. The advantage of theonline system to the patient is to eliminate the solution bags and thespace they consume. The dialysate, whether supplied from a sterilizedbag or made online, may also be recirculated in one or more loops usingone or more charcoal or sorbent cartridge.

One preferred at home generation system is described herein. That systemuses a reservoir, such as a five liter bag of sterile dialysateinstalled in a rigid container. A shunt is placed across the dialyzersat start-up for rinsing and priming. During treatment, a sorbentcartridge that operates using an urea exchange or a binding urea isplaced in the post dialyzer or ultrafilter (“UF”) loop. The sorbents mayremove other substances, such as beta 2 microglobulin or phosphate, etc.A series of infusion pumps simultaneously pull dialysate from thesterile bag, through a heater, through an ultrafilter and through theshunt to the sorbent cartridge. If necessary, an infusate such as agamma sterilized infusate that includes calcium, magnesium, andpotassium is added to the dialysate reservoir.

After the solution is heated and ready for treatment, the bloodtreatment machine prompts the user to install the cassette. The bloodcircuit can be primed with a saline bag hooked via the arterialbloodline or by backfiltering dialysate through the blood treatmentvenous filter. Air bubble detectors, heating elements, pressure sensors,temperature sensors, etc., are integrated into the cassette for both thedialysate and extracorporeal blood circuits as necessary to enable asafe treatment for the patient and a system that operates reliably.

The patient is then hooked to the arterial and venous needles and thetreatment begins. For short therapies, the dialysate flow can berelatively high, for example, three hundred ml/min for three hours orone hundred ml/min for up to eight hours. The dialysate/UF flow controlpumps control the flow to and from the dialyzers. By increasing thefrequency of the pumps that pull the effluent dialysate from thearterial dialyzer, the fluid accumulated in the patient in theinterdialytic period is removed. Portions of the dialysate/UF flowcontrol pumps are integrated into the cassette along with a portion ofthe blood pump in one embodiment or are alternately provided separatefrom the cassette and integrated into the machine.

Due to the impracticality of hanging and storing bags, solution-bagbased systems are limited to a total practical amount of dialysate pertreatment. The sorbent-based fluid regeneration system enables a therapythat uses more dialysate and thereby provides enhanced waste clearance.Providing an increased amount of dialysate beneficially enhances theclearance of waste products from the renal patient. For example, thesorbent cartridge could be used for a four hour treatment at two hundredto two hundred fifty ml/min dialysate flow or about fifty liters ofdialysate over the entire treatment, which would provide an increasedvolume of dialysate and better waste clearance over other hemofiltrationsystems. The sorbent system is also applicable to the hemofiltrationsystems described herein, making even predilution HF possible. Forhemofiltration, an additional reusable ultrafilter is provided tomaintain redundancy of bacteria and endotoxin removal.

The sorbent-based regeneration system is particularly suited for homeuse because it eliminates the need to store numerous solution bags,eases therapy setup and does not require a connection to the patient'swater tap. Also, the patient does not have to connect a tubing set. Thepatient instead places the cassette into the machine, adds an initialfive liter bag of sterile dialysate to the reservoir and starts theautomated priming sequence. When the priming is complete, the patientconnects himself/herself to the blood circuit and starts the dialysistherapy.

The portable device, the use of prepackaged solutions or an on-linefluid generation system and the use of a disposable set each providedialysis patients with the flexibility and freedom that previously hasonly been available to peritoneal dialysis patients. Because there is nodedicated water hookup and the present machines are small, it ispossible for a patient using the present systems to travel and performblood therapy dialysis sessions on the road. Many of the systems andmethods described herein can be adapted to work with in-centersolutions, and many of the aspects of the present invention are notlimited to home use.

High convection hemodialysis is believed to be more effective thanconventional hemofiltration because it has convective clearance inaddition to the diffusive transport of toxins. The therapy is expectedto provide good waste clearance of small, middle and large moleculesfrom even end-stage renal patients.

The device is well-suited for use in hospitals for acute patients forsituations in which a required water supply and dialysis proportioningsystem are unavailable. The present device is easier to set up and usein an intermittent acute setting.

The present invention provides multiple methods and apparatuses for notonly controlling the amount of dialysate or substitution fluid that isdelivered to the extracorporeal circuit or dialyzer but also foraccurately controlling the amount of ultrafiltrate removed from thepatient. The various alternatives can be divided into three main types.One type of control used is a pneumatic control based on Boyle's Law.Here, the fluid pumps are placed in fluid communication with a knownvolume of air. The system uses Boyle's Law to place into an equation aseries of known or measured values to calculate accurately the amount offluid (e.g., versus air) from a pump chamber pumped to the patient. Themethod and apparatus use fluid and air pressure signals generated andconverted to numbers that are placed into an equation.

The equation yields the fluid volume pumped per cycle or stroke of thepump. The Boyle's law system in one embodiment provides accurateinformation on an end stroke or pump cycle basis but not necessarily ona real time basis. The present invention also includes a system andmethod based on Boyle's Law that generates flow rate data on a real timebasis.

A second large category of volumetric control includes the use of abalancing device. Many embodiments for employing such balancing deviceare discussed below. The balancing device embodiments may be parsed intotwo main sub-groups. One sub-group uses a single balancing device.Another sub-group includes dual balancing devices.

The present invention also teaches and discloses a plurality ofdifferent types of balancing devices. In one embodiment, the systememploys one or two balancing chambers. In another embodiment, the systememploys one or two balancing tubes. The balancing tubes include atubular housing with a piston or ball-like separator within the housing.The separator acts similarly to the membrane or diaphragm of the balancechamber.

A third type of balancing device is one or more tortuous path. Thetortuous path is defined in one embodiment by a disposable cassette asan elongated channel. The diameter or cross-sectional area of thechannel is configured so that bulk movement of fresh or effluentdialysate can efficiently move an existing bulk of fluid within thetortuous path. That is, fresh dialysate in bulk moves a bulk of spent oreffluent dialysate currently residing in the path to drain. In the nextcycle, spent or effluent dialysate in bulk pushes the bulk of freshfluid just introduced into the tortuous path to the patient or dialyzer.The cross-section and the length of the path are configured to minimizean amount of mixing of the fresh and spent fluids at the ends of thebulks of fluid.

The various volumetric balancing devices can be used with many differenttypes of pumps, such as a peristaltic pumps, membrane pumps, gear pumpsor a combination thereof. A single pump may be used with the balancingdevices. Separate fresh and spent dialysate pumps may be usedalternatively. Further, a separate ultrafiltrate pump is alsocontemplated and discussed, which enables the main pump(s) to bededicated to pumping an equal volume of fluid to and from the patient.

The third major type of fluid management uses a scale to measure theamount of fluid delivered to the patient and the amount of fluid removedfrom the patient. In an embodiment illustrated below, fluid bags areplaced on a stand, which is coupled to a shaft. At one end, the shaftcouples to a rolling diaphragm. The rolling diaphragm, in combinationwith other apparatus, defines a closed but variable volume. As theweight in the fluid bags fluctuates, a pressure within the volume alsofluctuates. A pressure sensor senses the pressure and the controller orprocessor of the machine processes the signal from the pressure sensorto develop a corresponding weight signal. The weight signal is then usedto determine how much fluid has been delivered and or removed from thepatient. In one embodiment, fresh and spent fluid bags are measured bythe same weight sensing device, so that the system expects to see a netoverall weight gain over time due to the ultrafiltrate removed from thepatient. A load cell could also be used for this application.

As illustrated in detail below, the present invention provides multipleembodiments for other components of the systems and methods of thepresent invention, such as the fluid heater, the balancing devices, thedisposable cassette, bag positioning and other important features of thepresent invention. For example, the present invention includes an accessdisconnection sensor (“ADS”), which can detect when either the arterialor venous needle has been removed inadvertently from the patient duringtreatment. Further, various pressure relief schemes, integrity tests,etc., are discussed herein, which are important especially for ahome-use machine, which the patient may be use while sleeping.

It is therefore an advantage of the present invention to provide ahemodialysis, hemofiltration or hemodiafiltration system usable in ahome or clinic setting.

It is another advantage of the present invention to provide acassette-based hemofiltration/hemodiafiltration system, which enables apatient at home to easily set up a sterile blood therapy system.

It is another advantage of the present invention to improve theeffectiveness of renal failure blood treatment therapy.

Moreover, it is an advantage of the present invention to provide a renalfailure blood therapy that employs convective and diffusive modes ofclearance.

Still further, it is an advantage of the present invention to provide arenal failure blood therapy in which both diffusive and convectiveclearance modes are provided and wherein the percentage use of eithermode can be varied.

Further still, it is an advantage of the present invention to provide acassette-based blood therapy that is configurable in the field toperform either hemodialysis, enhanced convection hemodialysis,hemofiltration or hemodiafiltration.

Yet further, it is an advantage of the present invention to provide ablood therapy system with one or more therapy fluid circulation loopsthat optimize the consumption of fresh dialysate.

Still another advantage of the present invention is to provide a homerenal failure blood treatment therapy that is configurable to operatewith multiple different types of therapy fluid sources, such as solutionbags, solution preparation units or on-line dialysate generationsystems.

It is yet a further advantage of the present invention to provide a homerenal failure therapy system operable with many types of systems thatcontrol accurately the amount of fluid exchanges and the amount of fluidor ultrafiltrate removed from the patient.

Still further, it is an advantage of the present invention to provideimproved fluid volume control devices.

Additional features and advantages of the present invention aredescribed in, and will be apparent from, the following DetailedDescription of the Invention and the figures.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a schematic illustration of one embodiment of a renal failureblood treatment therapy system of the present invention that providesdiffusive and convective clearance modes.

FIGS. 2 and 3 are perspective views of one embodiment of a disposablecassette and associated flow components for use with the blood treatmenttherapies described herein.

FIG. 4 is a schematic illustration of a renal failure therapy systemthat operates with a dialysate fluid generation unit.

FIG. 5 is a schematic illustration of a renal failure blood treatmenttherapy system having a therapy fluid recirculation loop.

FIG. 6 is a schematic illustration of one embodiment of a home usehemofiltration system of the present invention.

FIG. 7 is a schematic view of another embodiment of a home usehemofiltration system of the present invention.

FIG. 8 is a schematic view of one embodiment of a home usehemodiafiltration system of the present invention.

FIGS. 9 to 11 show various embodiments of a home use blood treatmenttherapy that employs a regeneration unit that regenerates and reusesspent dialysis fluid and fluid ultrafiltered from the patient.

FIGS. 12 and 13 are alternative hemodialysis and hemofiltration systemsusing peristaltic pumps to pump the therapy fluid.

FIG. 14 is an alternative hemodialysis system, wherein the flow ofdialysate and blood are co-current.

FIGS. 15 and 16 are schematic views of one embodiment of a pneumaticallycontrolled method and apparatus for controlling the volume ofultrafiltrate removed from the patient.

FIGS. 17 to 22 are schematic flow diagrams of various embodiments forcontrolling the volume of ultrafiltrate removed from the patient via asingle balance chamber.

FIG. 23 is a schematic flow diagram illustrating various steps of oneultrafiltrate control method and apparatus employing a single balancetube.

FIG. 24 is a schematic flow diagram illustrating one embodiment forcontrolling the volume of fluid exchanged with the patient and thevolume of ultrafiltrate removed from the patient employing a singletortuous path.

FIGS. 25 and 26 are schematic flow diagrams illustrating variousfeatures and advantages associated with an ultrafiltrate control methodand apparatus that employs dual balance chambers.

FIGS. 27A to 27D are schematic flow diagrams illustrating the valveoperation and associated flow outcomes of another method and apparatusfor controlling the volume of fluid exchanged with the patient and thevolume of ultrafiltrate removed from the patient, which includes dualbalance tubes.

FIG. 28 illustrates one alternative valve arrangement for the balancetube volume control device of the present invention.

FIG. 29 is a schematic flow diagram illustrating yet another embodimentfor controlling the volume of ultrafiltrate removed from the patient,which includes dual tortuous paths.

FIGS. 30 and 31 illustrate yet a further alternative embodiment forcontrolling the amount of fluid that has been exchanged with and theamount of ultrafiltrate removed from the patient, which includes aweight measurement system.

FIG. 32 is an elevation view of one embodiment of an enhanced convectionof hemodialysis filter of the present invention.

FIG. 33 is a schematic view of one embodiment for the variable flowrestriction located between the dual dialyzers of the present invention.

FIG. 34 is a perspective view showing the cassette operably configuredwith flow actuation components of the dialysis systems of the presentinvention.

FIG. 35 is a perspective view of one embodiment for operably couplingthe solution bags to the renal failure therapy machine of the presentinvention.

FIGS. 36 and 37 are perspective views of embodiments for coupling thesolution bags to the renal failure therapy machine, which also show oneembodiment for enabling the machine to receive the cassette of thepresent invention.

FIG. 38 is a perspective view of an alternative embodiment for pumpingtherapy fluid employing linear tubing pumps.

FIG. 39 is a perspective view of one embodiment for operably couplingthe solution bags to a system using linear tubing pumps.

FIG. 40 is a schematic diagram showing one embodiment of a cassette ofthe present invention, which operates linear tubing pumps of the presentinvention.

FIG. 41 is a schematic illustration of another embodiment of a cassetteof the present invention, which operates with linear tubing pumps.

FIGS. 42 and 43 are sectioned perspective views of different alternativeimplementations of one embodiment of a fluid heater of the presentinvention.

FIG. 44 is a cutaway section view illustrating one embodiment forincorporating a balance chamber into a disposable cassette.

FIG. 45 is a perspective cutaway view of one embodiment of the balancetube of the present invention.

DETAILED DESCRIPTION OF THE INVENTION Overview

The present invention provides various apparatuses and methods for ahome hemodialysis (“HHD”) treatment that increases and enhances theamount of backfiltration during treatment. It is important to note thateven though this system is designed for the home, it is also suitablefor use in a clinic, acute renal treatment center or self-care center.The system uses a disposable fluid management system, which may includea disposable set having a disposable cassette or tubing organizer(referred to herein collectively as cassette). The cassette houses atleast a portion of at least one of the dialysate and extracorporeal flowpaths. In one embodiment, two small high flux dialyzers are connectedfluidly and in series to the cassette. In one embodiment, dialysate andblood flow in a countercurrent manner through the dialyzers with respectto each other. A restriction is placed between the two dialyzers in thedialysate flow path. The restriction is variable and adjustable in oneembodiment to account for different treatment conditions or to beadjusted during a single treatment. The restriction is alternativelyfixed, such as an orifice plate with a restricting orifice.

Due to the restriction between the filters, a positive pressure is builtin the venous dialyzer (first dialyzer to receive dialysate but seconddialyzer to receive blood in countercurrent arrangement), intentionallycausing a relatively high degree of backfiltration. Depending on thesize of the restriction between the dialyzers, that backfiltrationcauses a significant flow (e.g., 10 to 70 percent of total dialysateflow) of dialysate through the high flux venous membranes and into theblood circuit. The backfiltered solution provides convective clearance.In one embodiment, ultrafiltrate is removed from the patient via thearterial dialyzer (first dialyzer to receive blood but second dialyzerto receive dialysate in countercurrent arrangement).

The diffusion of dialysate into the venous dialyzer and removal ofdialysate from the arterial dialyzer causes a convective transport oftoxins from the patient. Additionally, the dialysate that does not movedirectly into the extracorporeal circuit (e.g., the other percentage ofthe dialysate) but instead flows across the membranes of both dialyzers,providing a diffusive clearance of waste products. This system, referredto herein as an enhanced convection hemodialysis (“ECHD”) system, issimilar to a hemodiafiltration system, which provides both convectiveand diffusive clearances. The system in one embodiment is configured forhome use, wherein at least a portion of the dialysate and extracorporealflow paths is sterilized and provided in a disposable set, which isloaded into a machine having multiple pumps, a heater, valve actuatorsand the like.

Enhanced Convection Hemodialysis (“ECHD”)

Referring now to the drawings and in particular to FIG. 1, oneembodiment of the renal failure therapy system 10 of the presentinvention is illustrated. System 10 employs two or more high fluxhemodialyzers, such as a venous dialyzer 20 and an arterial dialyzer 30.In one embodiment, hemodialyzers 20 and 30 are relatively small, e.g.,on the order of one quarter to three meters² of membrane surface area.Dialyzers or hemodialyzers 20 and 30 are relatively high flux dialyzers,e.g., having a UF coefficient of eight milliliters of water diffused perhour per millimeters Hg pressure or greater (as used herein, the term“flux” refers to the above UF coefficient, which measures the ease ofwater transport through the membrane, expressed inmilliliters/hour/millimeter Hg).

As discussed above, hemodialyzers 20 and 30 cause backfiltration in thevenous dialyzer 20 of a relatively large portion of the fresh dialysate.The backfiltered dialysate and the fluid accumulated during theinterdialytic period is ultrafiltered or removed from the patient 42 viathe arterial dialyzer 30. The fluid not backfiltered flows across thesemi-permeable membrane in the arterial 30 and venous 20 dialyzers,enabling system 10 to provide both diffusive and convective removal ofwaste from the patient's blood.

In one home use and in-center embodiment shown in FIG. 1, steriledialysate is stored in bags or containers 14, 16 and 18 (more than threesolution bags may be used). System 10 in the illustrated embodimentemploys pumps 22, 24, 26 and 28 that each operate with a respectivevolume measuring device 32, 34, 36 and 38. As described in detail below,various volumetric measuring devices are used alternatively with thesystems of the present invention. One measuring device is a capacitancefluid volume sensor that measures the volume of fluid pumped through oneof the pumps 22 to 28. That measurement in one embodiment informs acontroller or microprocessor how much fluid (or air) has been pumped.The controller or microprocessor compares the actual amount of fluidpumped to an expected amount of fluid pumped and adjusts the pumpingrates accordingly to make-up or back-off the delivery of new fluid todialyzers 20 and 30 as needed. Alternatively or additionally, thecapacitive measuring devices 32 to 38 can sense when a larger volumetricerror in the system occurs and trigger, for example, an error message(e.g., when air becomes trapped in the system or a majority of a strokelength is missed).

It should be appreciated that the present invention is not limited tocapacitive fluid volume measuring but can use instead other suitabletypes of volume measuring. Moreover, the present invention is notlimited to volume measuring but instead can employ balancing devicesthat ensure a set amount of dialysate is pumped to the dialyzers, fromthe dialyzers and from the patient 42. Further alternatively, fluid pumpmanagement can be accomplished on a mass basis, via one or more scale.Still further, flowrate and volume pumped can be calculated based on anumber of pump strokes, such as a number of peristaltic pump revolutionsbased on a number of steps of a stepper motor, based on a sensed amountof movement of a linear or rotating pump actuator or via a device thatoperates according to Boyle's Law. All of those measuring alternativesare included in the term “volume measuring device.” Control using thevolume measuring device can be closed loop, where the actual amount offluid delivered is monitored, or open loop, where the scheme relies onthe inherent accuracy of the pump and perhaps motion control feedback,such as a monitoring of number of step pulses sent to drive the motor,linear encoder feedback or rotary encoder feedback, etc.

FIG. 1 illustrates two pumps 22 and 24 for Pump Set 1 and two pumps 26and 28 for Pump Set 2. It is important to note that a single pump mayalternatively be used in place of each set of pumps, e.g., one to inputdialysate to the dialyzers and one to remove dialysate from thedialyzers and UF from the patient, however, that configuration wouldcreate pulsitile or uneven flow, which is less desirable. In theillustrated configuration, a first pump of each set is pulling fluidfrom the pump set's source, while a second pump of each set is pushingfluid towards the pump set's destination. After that set of pumpstrokes, the roles of the pumps in the respective sets alternate, sothat the first pump (now full of fluid) pushes fluid towards the pumpsset's destination, while the second pump (now empty) pulls fluid fromthe pump set's source. The above cycle is repeated multiple times.

Pump Set 1 inputs fresh dialysate from bags 14 to 18 to the system 10and Pump Set 2 removes a volumetric equivalent of the fluid pumped byPump Set 1 and any fluid removed from patient 42 during the course ofthe treatment. As illustrated, fresh dialysate is pumped via pumps 22and 24 from sources 14, 16 and 18 to the venous dialyzer 20. Arestriction 40 is located between venous dialyzer 20 and arterialdialyzer 30. Restriction 40 builds pressure in venous dialyzer 20, sothat a relatively large amount of fresh dialysate entering venousdialyzer 20 is forced through the walls of the membranes inside venousdialyzer 20 and into the extracorporeal or blood circuit 50. The otherportion of the fresh dialysate entering venous dialyzer 20 flows acrossthe membranes inside venous dialyzer 20, through restriction 40 and intoarterial dialyzer 30.

Convective clearance occurs when a volumetric equivalent of the fluidbackfiltered through venous dialyzer 20 is removed from the arterialdialyzer 30. Also, a diffusive transport of toxins occurs across bothdialyzers 20 and 30 due to a diffusive gradient that exists betweenblood circuit 50 and the flow of dialysate. Over the total therapy, thetotal amount of fluid removed from the arterial dialyzer 30 is greaterthan the total amount of dialysate supplied to the venous dialyzer 20,accounting for an amount of UF removal prescribed for the therapy.

Example

The following example further illustrates one preferred therapy for thepresent invention. In the example, pumps 22 and 24 of Pump Set 1 infuseeighteen liters of dialysate from sources 14, 16 and 18 over two hours.Of that volume, one hundred ml/min of dialysate is backfiltered into thepatient's blood circuit 50 through the membrane walls of venous dialyzer20. Fifty ml/min of dialysate passes through the venous dialyzer 20,restriction 40 and into venous dialyzer 30. Pumps 26 and 28 of Pump Set2 remove the total of eighteen liters of dialysate from bags 14, 16 and18 plus any desired amount of fluid from the patient. Over two hours,twelve liters (100 ml/min multiplied by 120 minutes) of dialysate isbackfiltered into the patient's blood through the venous dialyzer 20.Pumps 26 and 28 of Pump Set 2 remove that twelve liters, the six litersof dialysate that is not backfiltered into blood circuit 50 plus anyfluid ultrafiltered from the patient.

The addition and removal of the twelve liters of dialysate from bloodcircuit 50 over the two hour therapy yields an overall convectiveremoval according to the equation HF stdKt/V of ˜2, which has beenreported to be a suitable daily amount (see Jaber B T, Zimmerman D L,Leypoldt J K. Adequacy of Daily Hemofiltration: Clinical Evaluation ofStandard Kt/V (stdKt/V), Abstract Hemodialysis International Volume 7,number 1, p80, 2003. Additionally, over the course of two hours, sixliters of dialysate was used for diffusive clearance via the dialysategradient across the membranes of dialyzers 20 and 30. Note that thedialysate flow rates and percent convective versus diffusive could behigher or lower than those used in the example.

Introduction to Disposable Cassette

Referring additionally to FIGS. 2 and 3, dialyzers 20 and 30 as well asmany other flow components described herein are provided in onepreferred embodiment attached to a disposable cassette. Disposablecassette 100 a can otherwise be referred to as an organizer, disposable,disposable set, etc. Disposable cassette 100 a includes at least aportion of the extracorporeal circuit 50 and dialysate flow path 60 (seeFIG. 1) for the renal failure therapy treatment (e.g., all ofextracorporeal circuit 50 is integrated into cassette 100 a with theexception of the tubing going to and from the patient as illustrated inFIGS. 2 and 3). Disposable cassette 100 a provides a space efficientapparatus for handling the dialysate or therapy fluid flow portions ofthe many pumps and valves described herein, which are actuatedpneumatically or mechanically as described below. Cassette 100 a istherefore well suited for home use, where space, capability andresources are limited.

In one preferred embodiment, disposable cassette 100 a and associatedattached tubing are gamma sterilized and sealed prior to use.Alternatively, sterilization via ethylene oxide or ebeam is employed.The patient or operator opens the seal just prior to use, insertscassette 100 a into the therapy machine for a single use and thendiscards the cassette 100 a and associated tubing. While cassette 100 aand flow paths 50 and 60 are intended for a single use in oneembodiment, cassette 100 a and flow paths 50 and 60 could be reused withsuitable disinfection and/or sterilization.

Incorporation of Cassette and ECHD System

Referring to FIGS. 1 to 3, beginning from the arterial access 44 a ofthe patient 42, the extracorporeal or blood circuit 50 includes apressure sensor 46, labeled PT1. PT1 is alternatively a pressure switchwith the ability to stop blood flow prior to reaching blood pump 48. Asa safety measure, system 10 in one embodiment includes a multitude ofelectrodes (not shown), such as two to four electrodes, which provide anaccess disconnection sensor, which is integrated half in the arterialline 44 a and half in the venous line 44 b to detect accessdisconnection of patient 42 from the system 10. An alternative mechanismfor detection of accidental needle disconnections is the use of aconductive blanket underneath the patient's access. The presence ofblood changes the conductivity of the blanket and sets off an alarm andstops the pumps.

Blood pump 48 is peristaltic pump 48 in one embodiment and is locatedbetween pressure sensor PT1 and a drip chamber 52 a with integralpressure transducer 46, labeled PT2. The drip chambers 52 a to 52 cremove air from the fluids passing through the drip chambers. One, amultiple of or all the drip chambers 52 a to 52 c in an alternativeembodiment includes an associated level sensor 68 a to 68 c. Thosesensors are connected to or integrated into the associated dripchambers. Level sensors 68 a to 68 c sense and indicate the level orheight of dialysate or therapy fluid in the dialyzer. Blood pump 48 isalternatively a volumetric pumping device other than a peristaltic pump,such as a diaphragm pump or centrifugal pump. Blood pump 48 can also bebidirectional for system priming as discussed below. Pressure sensor PT246 is alternatively not associated with a drip chamber, where forexample pressure transducers are used instead. Pressure sensors PT1 andPT2, drip chamber 52 a as well as the tubing 102 for peristaltic pump 48are all connected to cassette 100 a.

After drip chamber 52 a, blood flows out of the housing 104 of cassette100 a into a the relatively small, high flux dialyzer arterial dialyzer30. As seen in FIG. 2, arterial dialyzer 30 and venous dialyzer 20 areattached to an end of housing 104 of cassette 100 a. Blood then flowsfrom the arterial dialyzer 30 to the venous dialyzer 20, back intohousing 104 of cassette 100 a and through a second drip chamber 52 b.Drip chamber 52 b also has an integral pressure sensor 46, labeled PT3.PT3 is alternatively provided without a drip chamber when, for example,pressure transducers that coupled directly to the line are used instead.

An air bubble detector 54 labeled ABD is located downstream from dripchamber 52 b in blood line 50. A venous line clamp or valve 56, labeledV1, which may be cassette-based or provided external to cassette 100 a,and which shuts down blood flow if air is detected in line 50 bydetector 54, is located between the air detector 54 and arterial access44 b, which returns blood to patient 42. An air level sensor (notillustrated) on drip chamber 52 b is used alternatively or in additionto ABD 54. To detect air in the blood, a level detect scheme isalternatively or additionally provided with drip chamber 52 b orpressure transmitter 46, labeled PT3. For example, an ultrasonic sensorcan be placed on opposite sides of the drip chamber. The sensorgenerates a signal that depends upon the percentage of air in the bloodthat passes between a transmitting and receiving positions of thesensor. Under normal operation, when no air is present, the blood withindrip chamber 52 b resides at a relatively steady level, although levelfluctuations do occur due to changes in pressure, amount of bloodpumped, etc. A threshold level of blood in chamber 52 b does exist belowwhich the blood should not drop. When air in the blood lines is present,the blood level in the chamber 52 b is lower than a threshold level,triggering an alarm from the alternative air/blood detector. It isimportant to note that an air detector and line clamp may be used online 44 a, if required by rinse, prime or blood rinseback.

Dialysate flow path 60 is also located primarily in the housing oforganizer or cassette 100 a. The dialysate is supplied initially indialysate or therapy fluid supply bags 14, 16 and 18. In alternativeembodiments shown below in connection with FIGS. 4 and 9 to 11, thesource is an on-line source or other type of non-prepackaged source. Inthe embodiment illustrated in FIG. 1, a minimum of one infusion bag isprovided and in one preferred embodiment multiple bags, such as threesources 14 to 18 are provided. FIG. 1 also illustrates that the systemis provided initially with an empty drain bag 12, which is filled withspent solution from the supply bag 14, 16 or 18 that is used first.After the first two supply bags 14, 16 or 18 are drained, they becomethe drain bags for the second and final solution bags, respectively.Because the therapy in the end removes more fluid than is inputted, eachof the supply bags 14 to 18 is used to receive spent fluid and UF. Thebag sequencing is controlled as illustrated by valves 56, labeled V8 toV14.

Dialysate or therapy solution flows from one of sources 14 to 18 to thevolumetric diaphragm pumps 22 and 24 of set 1. The volumetric accuracyof the pumps is confirmed by monitoring. As discussed above, it isdesirable to use two alternating solution delivery pumps 22 and 24 tolimit the amount of pulsitile flow. As a safety measure, the diaphragmsof each of the pumps 22 to 28 are configured so that if they leak, thecan only leak externally. Any leaks collected externally from pumps 22to 28 is then diverted towards a moisture sensor built into the cassette100 a, machine and/or cassette/machine interface, which senses such leakand signals: (i) an alarm; (ii) to shut down pumps 22 to 28 and 48; and(iii) to take any other appropriate action.

Suitable pneumatically and mechanically driven medical fluid pumps anddiaphragms therefore are described in commonly owned U.S. Pat. No.7,238,164, entitled Systems, Methods And Apparatuses For PumpingCassette-Based Therapies, filed Dec. 31, 2002, the teachings of whichare incorporated herein by reference. The pumps and pumping technologycurrently used in the HomeChoice® series of APD devices, as embodied inU.S. Pat. No. 5,431,626 and its associated family of patents, theteachings of each of which are incorporated herein by reference, arealso suitable, as are various pumping technologies described in commonlyowned U.S. Pat. No. 6,814,547, entitled “Medical Fluid Pump”, filed May24, 2002, the teachings of each of which are incorporated herein byreference.

As discussed above, each of the pumps 22 to 28 operates individuallywith a volume measuring device 32 to 38. In one preferred embodiment,volume measuring devices 32 to 38 are capacitance fluid volume sensors,indicated in FIG. 1 by dashed lines representing the associatedcapacitor plates. One embodiment of a capacitance sensor is disclosed ingreater detail in the U.S. Patent entitled, “Capacitance Fluid VolumeMeasurement,” U.S. Pat. No. 7,107,837, filed on Jan. 22, 2002,incorporated herein by reference. That capacitance sensor usescapacitance measurement techniques to determine the volume of a fluidinside of a chamber. As the volume of the fluid changes, a sensedvoltage that is proportional to the change in capacitance changes.Therefore, the sensor can determine whether the chamber is, for example,empty, an eighth full, quarter full, half full, full, or any otherpercent full. Each of these measurements can be made accurately, forexample, at least on the order of the accuracy achieved by knowngravimetric scales or pressure/volume measurements. Capacitance sensing,however, is simpler, non-invasive, inexpensive and is operable withcontinuous, non-batch, type pumping operations.

Generally, the capacitance C between two capacitor plates changesaccording to the function C=k×(S/d), wherein k is the dielectricconstant, S is the surface area of the individual plates and d is thedistance between the plates. The capacitance between the plates changesproportionally according to the function 1/(R×V), wherein R is a knownresistance and V is the voltage measured across the capacitor plates.

The dielectric constant k of medical fluid or dialysate is much higherthan that of air, which typically fills a pump chamber (such as pumpchambers 122, 124, 126 and 128 in FIG. 2, which are part of pumps 22 to28 in FIG. 1) that is empty or at the end of a pump out stroke. In oneembodiment, one of the capacitance plates is moveable with the volume offluid entering or exiting the chambers 122, yielding the changingdistance, Δd, between the plates a factor in determining capacitance.Likewise the surface area, S, of the capacitance plates could be varied.In one preferred embodiment shown figuratively in FIG. 1, thecapacitance plates 32, 34, 36 and 38 are set at a fixed distance fromone another, e.g., are fixed to the rigid plastic of housing 104 ofcassette 100 a. In that instance, the surface area S is also fixed,leaving the change in the dielectric constant k to account for thechange in capacitance as the pump chambers 122 to 128 are filled oremptied of dialysate.

As at least one flexible membrane positioned within chambers 122 to 128expands and fills with medical fluid, the overall capacitance changes,i.e., increases, creating a high impedance potential across thecapacitor plates, one of which is grounded, the other of which isactive. That high impedance potential is indicative of an amount offluid in the chambers 122 to 128. If the sensed potential does notchange, or does not change enough, when it is expected to change, thesystem controller recognizes such lack of change as air that has becometrapped in the dialysis fluid and commands appropriate actions.

A capacitance sensing circuit is provided, which amplifies the highimpedance signal to produce a low impedance potential. The low impedanceis fed back to the capacitance plates 32 to 38 and is used to protectthe sensitive generated capacitance signal from being effected byoutside electrical influences. The amplified potential is also convertedto a digital signal and fed to a the system controller, where it isfiltered and or summed. A video monitor having a graphical userinterface can then be used to visually provide a volume and/or aflowrate indication to a patient or operator based on the digitalsignal. Additionally, the controller uses the flowrate and volumeinformation to ensure that Pump Set 2 (pumps 26 and 28) withdraws theappropriate amount of fluid from arterial dialyzer 30, namely, theamount of dialysate pumped from Pump Set 1 (pumps 22 and 24) plus theprescribed amount of UF removed from the patient.

An additional use for capacitance plates or volume measuring devices 32to 38 is to detect a leak across pump valves V3 and V5, V2 and V4, V15and V16 and/or V17 and V18. Those valves cycle and alternate during thepump-in and pump-out strokes of pumps 22, 24, 26 and 28, respectivelyand are opening and closing much more often than other valves in system10, such as fluid container valves V8 to V14. The pump valves aretherefore more susceptible to leakage than are other valves and arerelatively critical to the operation of system 10.

The pump valves operate in alternating pairs. For instance, to deliverfluid into pump 22, valve V3 is opened while valve V5 is closed.Conversely, to push fluid from pump 22, valve V3 is closed while valveV5 is opened. If both valves are either opened or closed while a pumpstroke takes place, volumetric error occurs. The present inventioncontemplates a method and apparatus for testing valves V3 and V5, usingvolume measuring devices 32 to 38.

The valve test in one embodiment utilizes the fact that the pump hasflexible fluid membranes that are crimped between a fixed volume pumpchamber. When a pump-in stroke takes place, the membranes fill withfluid expanding the membrane. The corresponding pump inlet valve (e.g.,valve V3) is then closed, trapping fluid within the flexible pumpchamber membranes. A partial pump-out stroke is attempted either via amechanical piston or positive/negative pneumatic pressure. The pressureexerted is not enough to damage the pump components but is enough sothat if either inlet or outlet valves (e.g., V3 and V5) is faulty orleaking, fluid would flow, creating a volume change that would be sensedby volume measuring devices 32 to 36.

If the valves close properly, and assuming dialysate to beincompressible, the small pressure exerted should move no fluid andproduce no detectable volume change. If a leak is present, a volumechange occurs and is detected, causing the controller to issue an alarmcondition or take other appropriate action. The above-described test canbe performed at the start of therapy and/or intermittently andperiodically throughout therapy, e.g., every five minutes or every onethousand strokes. The test, it should be appreciated, can at leastdetect which set of pump valves V3 and V5, V2 and V4, V15 and V16 or V17and V18 is leaking. The test is applicable to all types of medical fluidsystems, including blood therapy systems, congestive heart failuresystems and peritoneal dialyzer systems.

The chambers 122 to 128 and housing 104 of cassette 100 a form a firstportion of a clamshell, the second portion being formed by the renaltherapy machine. The first and second portions house at least oneflexible membrane and the dialysate when dialysate is present. Theportions are rigid and form a fixed volume in one preferred embodiment.The portions form the shape of and also house the capacitor plates 32 to38. That is, one of the capacitor plates is housed in cassette 100 a,while the other is housed inside the therapy machine. Alternatively,both plates are housed in the therapy machine, one on either side of thecassette. As stated above, either the cassette or machine (whicheverhouses the active rather than the ground capacitor plate) houses anadditional guard or shield plate that provides noise protection for thehigh impedance signal transmitted from the active capacitor plate.

As an alternative to the capacitance volume sensor described above, thevolume or mass of dialysate fluid flowing through the pumps 22 to 28 canbe determined using other methods, such as through an electronic scaleor balance. In other alternative embodiments, the mass or volume ofdialysate flowed in any of the systems described herein can be sensedusing various types of medical grade flowmeters, orifice plates, massflow meters or other devices employing Boyle's Law. Further, the FluidManagement System (“FMS”) technology used in HomeChoice®, as embodied inU.S. Pat. No. 5,431,626 and its associated family of patents, theteachings of each of which are incorporated herein by reference, is alsosuitable for use in the present invention. A pneumatically controlledsystem employing this technology is discussed in more detail below.Conductivity sensors may also check for conductive and nonconductivestates across the valves, detection of valve leaks is easy with thismethod.

Still further alternatively, fluid balancing chambers or match flowequalizers may be used, such as those described in U.S. Pat. No.5,486,286, assigned to the assignee of the present invention,incorporated herein by reference, which are also employed in the System1000™ produced by the assignee of the present invention. The balancingchambers or flow equalizers are integrated in the cassette in oneembodiment and require a separate pump or pressurization source. Thechambers or equalizers would manage fresh dialysate on one side of adiaphragm and the spent dialysate on the other side of the diaphragm,matching the volume flow of fresh and spent dialysate. A separate pumpis then used to ultrafiltrate fluid from patient 42 accumulated betweenpatient sessions. Peristaltic pumps may also be used to pump dialysateto dialyzers 20 and 30 or to any of the blood filtering devicesdescribed herein, pump an equal amount of fluid from such devices,control and pump out a prescribed amount of ultrafiltrate from thepatient. One suitable peristaltic pump arrangement is illustrated belowin connection with FIG. 12. Systems employing balancing chambers andother volumetric control devices are discussed in more detail below.

Referring still to FIGS. 1 to 3, valves 56 labeled V2, V3, V4 and V5control which pump is filling and which pump is exhausting dialysate atany given time. Those valves, as well as most if not all the valves ofthe systems described herein have an electromechanical portion housedinside the blood treatment machine and a fluid flow portion 156, shownin FIG. 2. Dialysate or renal therapy fluid exiting pumps 22 and 24enters a heater 58. Heater 58 is located alternatively prior tovolumetric diaphragm pumps 22 and 24. Heater 58 may be any suitable typeof electrical medical fluid heater, such as a plate (electricalresistance) heater, infrared or other radiant heater, convective heater,and any combination thereof. Heater 58 is illustrated as an in-lineheater. As seen in FIG. 2, dialysate flows through a flexible membraneheating portion 158 of cassette 100 a. The electronics and otherhardware associated with heater 58 are located inside the renal failuretherapy machine. Heater 58 is located alternatively to batch heatsolution bags 14, 16 and 18.

Valve 56 labeled V6 provides a bypass that enables solution at too highor too low a temperature to be diverted to a point upstream of pumps 22and 24 to prevent solution at too high/low a temperature from reachingthe dialyzers 20 and 30 and ultimately blood circuit 50. To that end,temperature sensor 62 labeled T2 senses and provides feedback to thecontroller of system 10 indicating the temperature of dialysate leavingheater 58. The temperature sensor 62 could be a thermocouple or IRsensor or thermistor, which is housed inside, integral with or directlyadjacent to a conductivity sensor probe 63. Conductivity sensing istemperature dependent, so it is logical to locate the two sensors 62 and63 together or directly adjacent to each other.

A suitable location for the temperature sensor/conducting sensor is, forexample, at sensor location T2, T3 which senses the conductivity of thefluid prior to the fluid reaching dialyzers 20 and 30. Conductivitysensor 63 may be used to test the electrolyte composition of thesolution. Conductivity sensor or electrolyte sensor 63 is particularlyuseful when using a dual chamber version of containers 14, 16 and 18,which have multiple solution components that are mixed just prior touse.

A pressure sensor 46 labeled PT4 measures the pressure of the fluidflowing to venous dialyzer 20 and in one embodiment is provided inassociation with an additional drip chamber 52 c that purges air throughvent 64 c and vent valve 56 labeled V19. Sensor PT4 and chamber 52 c arelocated alternatively prior to volumetric diaphragm pumps 22 and 24.

The dialysate next flows into venous dialyzer 20. The membranes housedinside venous dialyzer are high flux membranes as discussed above. Thedialysate flow path connects to the venous 20 and arterial 30 dialyzersvia the restriction 40. Restriction 40 provides backpressure that drivesa significant amount of the dialysate through the high flux membranes ofthe venous dialyzer 20 and directly into the blood flowing through themembranes inside venous dialyzer 20. Restriction 40 can be set tobackpressure ten to ninety percent of the dialysate entering venousdialyzer 20 into the bloodline. As discussed above, restriction 40 canbe set or variable. If a fixed restriction is desired, it is possible touse a single dialyzer rather than the two dialyzers 20 and 30 shown inFIG. 1. A dialyzer having an internal flow restriction suitable for usein place of items 20, 30 and 40 shown in FIG. 1 is described in commonlyowned U.S. Pat. No. 5,730,712, entitled “Extracorporeal Blood TreatmentApparatus and Method”, incorporated herein by reference. That dialyzeras indicated is limited to having a fixed orifice.

As alluded to above, it is desirable for a number of reasons thatrestriction 40 be a variable restriction. For one reason, differentpatients may respond to a therapy that is more convective or morediffusive. From a cost and manufacturing standpoint, it is desirable tohave a unit that can be adjusted for any patient rather than “custom”units fitted with the necessary flow restriction. Second, it is verypossible that the patient and doctor will not know initially what theoptimal percentage convective clearance versus diffusive clearancebreakdown is, requiring some period of experimentation and optimization.Moreover, it may be desirable for a patient to perform a first treatmentusing a first percentage convective clearance versus diffusive clearanceand later in the week, the next day or later in the same day perform asecond treatment using a different percentage convective clearanceversus diffusive clearance.

Still further, system 10 has the capability of varying the percentageconvective clearance versus diffusive clearance over a single therapysession or treatment, for example in step increments or continuously.Such changes can be made as gradually or quickly as desired and span asgreat a range as desired, e.g., starting with 90 percent convective andending with 90 percent diffusive. It may be determined that it isdesirable to clear molecules of a particular size or range of sizes ormolecules of a particular type during a certain point in the therapy,e.g., at the beginning or end. Variable restriction 40 also makes itpossible to repeat certain settings or patterns of settings during asingle treatment.

The present invention contemplates at least three levels of variabilityfor restriction 40. The first level can be referred to as “semi-fixed”.Here, the restriction could use a fixed orifice restriction plate, butwherein restriction 40 is configured and arranged so that the plate canbe swapped out for a plate having a different sized orifice. Suchswapping out would occur, however, between therapies. A second level ofvariability can be referred to as “manual-on-the-fly”. Restriction 40 inthis instance could be a backpressure regulator or variable orificevalve with a manual adjustment that enables the patient or operator toadjust the backpressure and thus the convective versus diffusiveclearance percentage. The manual adjustment could be made during acurrent therapy or between therapies. The third level of variability isautomatic, which could be effected for example via a pneumaticallyoperated backpressure regulator or variable orifice valve. Suchpneumatically operated device receives a pneumatic signal at acontrolled pressure, which sets the backpressure accordingly. Thecontroller could be configured to output for example an analog signal,e.g., a 0-5 VDC or 4-20 mA signal, which is converted via an I/Pconverter to a pressure signal at a corresponding pressure. Theautomatic adjustment could be made during a current therapy or betweentherapies.

Referring still to FIGS. 1 to 3, Pump Set 2 including pumps 26 and 28resides on the exit end of arterial dialyzer 30. Each of the variousembodiments described above for Pump Set 1, including the pumpconfiguration, is applicable for Pump Set 2. Pump Set 2 is normallyconfigured to pump at the rate of the fresh dialysate input of Pump Set1 plus an additional amount to remove excess fluid that has accumulatedin the patient's blood and tissues between treatment sessions.

The waste dialysate and a volumetric equivalent to the patient's fluidgained in the interdialytic period flows from arterial dialyzer 30,through valves 56 labeled V16 and V18, through pumps 26 and 28, throughvalves 56 labeled V15 and V17, through a blood leak detector 66 and toen one of the drain bags 12 to 16, which as discussed above are openedselectively via valves 56 labeled V9 to V14. Valves 56, detector 66 andfluid contacting portions of pumps 26 and 28 are each in one embodimentlocated in the housing portion 104 of cassette 100 a. The waste and avolumetric equivalent to the patient's UF may alternatively be routedafter BLD 66 to a long tube placed in an acceptable drain. Thisalternative will not work with balance scale systems.

Blood leak detector 66 includes in one embodiment a light source and aphoto sensor. Blood components that are not meant to be filtered throughdialyzers 20 and 30 lower the light reaching the photo sensor ofdetector 66 if such components do travel through the membrane walls ofthe dialyzers into the therapy solution flow path. The controller ofsystem 10 continuously monitors the photo sensor. Detection of a bloodleak triggers an audio and/or visual alarm, stops blood pump 48 andcloses venous line valve V1. A blood sensor, such as detector 66, isalternatively or additionally placed in the venous line running fromvenous dialyzer 30 to pumps 26 and 28.

In special modes, infusion pumps 22 and 24 of Pump Set 1 can infuse moresolution than is removed to drain by pumps 26 and 28 of Pump Set 2. Forexample, during priming, during blood rinseback or for bolus infusion,infusion pumps 22 and 24 can infuse a volume that is greater than thevolume removed by pumps 26 and 28. The special modes enable the systemto fill with fluid, enable blood in line 50 at the end of therapy torinseback to the patient 42 or for the patient 42 to receive a bolus ofsolution via the venous dialyzer into the post dialyzer portion ofcircuit 50 and through venous access 44 b to patient 42.

During priming, the arterial and venous needles 44 a and 44 b areconnected together as seen in FIG. 2. The pumps of Pump Sets 1 and 2 arerun until air is purged from the system, so that only (or substantiallyonly) dialysate flows throughout the dialysate flow path 60. When bloodpump 48 begins pumping, dialysate and/or saline is backfiltered fromvenous dialyzer 20 into blood line 50, priming the remainder of theextracorporeal circuit 50. An alternative or additional form of primingis to connect a bag of saline at arterial access 44 a.

In one embodiment, blood is returned to the body by reversing the flowdirection of blood pump 48, which would require an additional air/blooddetector and clamp, such as ABD 54 and clamp V1 placed in line 44 a,between pump 48 and patient 42. Blood pump 48 would run in reverse untilthe additional air blood sensor detected an absence of blood in line 44a. Pump 48 would be reversed again to flow fluid in the normaldirection, which would return filtered dialysate and blood to patient 42until the absence of blood is sensed in the venous line 44 b.Alternatively, this same method of blood rinseback may be employed butthe air blood sensor would only be used to confirm the absence of blood,but the rinse controlled by pre-set dialysate and/or saline volume.

Alternative Source Fluid Preparation Module

Referring now to FIG. 4, an alternative system 110 is provided thatoperates in a very similar manner to the system 10 described above.Indeed, each of the like reference numerals shown in FIGS. 1 and 4 havethe same functionality and the same alternatives as describedpreviously. System 110 performs convective and diffusive clearance asdescribed above and removes the amount of fluid gained by patient 42between therapy sessions.

System 110 differs from system 10 in that system 110 does not usesolution bags 14 to 18 and drain bag 12, instead, system 110 operateswith and connects to a separate fluid preparation module 112. System 110is advantageous because patient 42 is not required to store, connect to,disconnect from and discard multiple solution bags as described above.As seen by comparing systems 10 and 110, system 110 eliminates multiplevalves 56 (V9, V10 and V12 to V14) by using an on-line dialysategeneration source 112.

One suitable fluid preparation module 112 suitable for home use iscommercially available from PrisMedical, however, other systems having awater purification pack and electrolyte cartridge to prepare thedialysate could be used. System 110 alternatively uses a large, e.g.,about 120 liters, fill bag or fill container (not illustrated), whichreceives dialysate or therapy fluid from the preparation module 112.System 110 is also compatible with an in-center environment, wherein asingle patient or central fluid preparation module 112 supplies a singleor multiple systems 110. The single patient or central proportioningmodule could prepare dialysate or substitution fluid using aproportioning system. For an in-center use, it is contemplated not touse cassette 100 a but instead provide a machine that can be sterilizedand re-used. In any of the above-described embodiments for system 110,the system pumps waste dialysate and UF to a waste dialysate bag, wastecontainer, drain or waste area 114.

Addition of Regeneration Loop

Referring now to FIG. 5, an alternative system 210 is provided that addsa regeneration loop 212 to the dialysate flow path. As with FIG. 4, eachof the like reference numerals shown in FIGS. 1, 4 and 5 have the samefunctionality and the same alternatives as described previously. System210 also performs convective and diffusive clearances as described aboveand removes an amount of fluid or ultrafiltrate gained by patient 42between therapy sessions.

Regeneration loop 212 includes an additional pump 214, which operateswith an associated volumetric measuring device 216. Any of theembodiments described above for pumping, measuring flow and controllingflow may be employed for pump 214 and measuring device 216. Additionalinlet and outlet valves 56, labeled V22, V23 and V26 are provided toallow or disallow flow of spent dialysate/UF from arterial dialyzer 30to be pumped to pump 214. As illustrated, pump 214 can pump to therecirculation sorbent cartridge 222 or to drain. Additional outletvalves 56, labeled V24 and V25, are connected fluidly to UF pumps 26 and28, so that those pumps can pump selectively to drain or to therecirculation sorbent cartridge 222. In short, any combination of pumps26 and 28 can be used repeatedly or at different times during therapyfor recirculation or ultrafiltration.

As illustrated, pump 214 is configured to pump spent dialysate/UF backto the inlet of arterial dialyzer 30 via line 220. Line 220alternatively runs to the inlet of venous dialyzer 20, wherein theregenerated fluid is reintroduced into that dialyzer. Moreover,regenerated fluid could be pumped to both of the inlets of venousdialyzer 20 and arterial dialyzer 30. Still further, it is possible toregenerate fluid exiting venous dialyzer 20 alternatively oradditionally to the regeneration of fluid exiting arterial dialyzer 30.

In system 210, the total amount pumped through UF pumps changes due tothe additional recirculation pump 214. In the example given above, pumps26 and 28 of Pump Set 2 were said to remove eighteen liters of dialysateadded over the course of the therapy (wherein twelve liters was used forconvective clearance, while six liters of dialysate was used fordiffusive clearance) plus any fluid ultrafiltered from the patient.

Applying the eighteen liters used in the above Example to system 210,and assuming twelve liters is used to produce convective clearance, theremaining six liters plus the volume of fluid that is recirculatedthrough recirculation loop 212 is then used to produce diffusiveclearance. If pumps 26, 28 and 214 are configured so that one-third ofall fluid exiting arterial dialyzer 30 is recirculated, then 225 ml/minis pulled from arterial dialyzer 30, 75 ml is passed throughrecirculation loop 212 and 150 ml is discharged to the drain bags 12, 14and 16. The diffusive clearance is calculated to be the six liters ofsingle pass dialysate plus 75 ml/min of recirculation loop 212 dialysatefor 120 minutes, or six liters plus nine liters, totaling fifteen litersof diffusive clearance. If pumps 26, 28 and 214 are each operated at 100ml/min, one-half of all fluid exiting arterial dialyzer 30 isrecirculated through recirculation loop 212 and the diffusive clearanceincreases to six liters plus 150 ml/min for 120 minutes or six litersplus eighteen liters, totaling twenty-four liters of total diffusiveclearance.

The trade-off for the increased clearance is that a sorbent cartridge222 is required in recirculation loop 212 to clean or regenerate thespent dialysate/UF pulled exiting arterial dialyzer 30. Depending onquantity and quality needed for the regenerated fluid, cartridge 222 maybe as simple as a carbon cartridge but is alternatively a multilayercartridge with Urease (similar to the cartridges described in U.S. Pat.Nos. 3,669,880 and 3,669,878, the teachings of which are incorporatedherein by reference). Other suitable cartridges and materials thereforeare discussed in commonly owned U.S. patent application Ser. No.10/624,150, entitled, “Systems And Methods For Performing PeritonealDialysis” and commonly owned U.S. Pat. No. 7,208,092, entitled, “SystemsAnd Methods For Peritoneal Dialysis”, the teachings of each of which areincorporated herein by reference. Depending on the type of sorbent usedin cartridge 222, system 210 as well as any other system describedherein that uses sorbents may require a sterile infusate additive 616 online 220 to replace electrolytes lost in the sorbent cartridge and aconductivity temperature sensor 62, 63 to measure the electrolytesindependently of the infusion.

In general, the cleaning cartridges remove waste products from the spentfluid and improve the efficiency of same for causing diffusive transportof toxins. Sorbent cartridge or cleaning cartridge 22, can employ one ormore different types of cleaners or exchangers, such as an activatedcharcoal filter, a sorbent exchange, a chemical cleaner, a chemicalexchange, a biological cleanser, a binding adsorption agent, anenzomatic reaction agent, a mechanical cleaner and any combinationthereof.

Cassette-Based Hemofiltration System

Referring now to FIGS. 6 and 7, systems 310 and 410, respectively,illustrate that the cassette-based home system is configurablealternatively to perform pure hemofiltration. The primary differencesbetween systems 310 and 410 versus systems 10, 110 and 210 describedabove are that the pure hemofiltration systems do not use the venousdialyzer 20 and the restriction 40, which may simply be removed from orbypassed in cassette 100 a to form hemofiltration system 310 or 410.Arterial dialyzer 30 in FIG. 1 then operates as hemofilter 312 in system310 or 410. Arterial dialyzer 30/hemofilter 312 is therefore chosen tobe able to perform both roles.

The remainder of system 310 is configured by disconnecting the line 314(shown in FIG. 1) from venous dialyzer 20 (FIG. 1) and reconnecting theline to postdilution line 316 in FIG. 6. Such disconnection andconnection and can occur either in housing 104 of cassette 100 a or viatubing connected to cassette 100 a. The present invention accordinglycontemplates expressly the provision of a cassette that can either befactory set or be set in the field or at home by the patient forhemofiltration or for the backfiltered hemodiafiltration (“HDF”) therapydescribed above.

A check valve 326 is placed in line 314 to prevent blood from backing upinto pumps 22 and 24. A similar check valve 326 can be used in ananalogous location in any hemofiltration or HDF embodiment describedherein, e.g., FIGS. 6 to 8 and 11. Optional shunt line 324 and valve 56,labeled V20, may be used so that predilution and postdilution HF can beperformed selectively individually or simultaneously with system 310 andother systems shown below.

System 310 as illustrated is a postdilution hemofiltration device,wherein fluid from infusion pumps 22 and 24 is injected directly intothe postdilution bloodline 316, which is located downstream ofhemofilter 312. In an alternative embodiment, fluid from infusion pumps22 and 24 is injected directly into the predilution bloodline 318, whichis located upstream of hemofilter 312. In such a case, the fluid in onepreferred embodiment is injected at or upstream of drip chamber 52 a toprevent air from entering filter 312. Predilution and postdilution bothhave particular advantages over one another.

Postdilution provides better clearance per liter of substitutionsolution than does the predilution clearance mode. Postdilutionclearance per liter of substitution fluid can, for example, be twice aseffective as predilution clearance. Postdilution blood flow ratelimitations, however, restrict the total amount of substitution fluiddue to the risk of hemoconcentration. Predilution allows for higherclearance rates because the volume of substitution fluid is not limitedby hemoconcentration. Therefore, the overall clearance over a given timecan be, albeit less efficiently, greater using predilution therapy thanfor postdilution therapy.

FIG. 7 illustrates another alternative embodiment for a hemofiltrationsystem of the present invention. System 410 of FIG. 7 illustrates that afirst dialysate line 320 extends from the output of postdilutioninfusion pump 22 and feeds directly into postdilution line 316, whichexits hemofilter 312.

A second line 322 extends from the output of predilution pump 24 to thedrip chamber 52 a placed just in front of predilution line 318, whichextends to the input of hemofilter 312. Check valves 326 are placed inboth lines 320 and 322 to prevent blood from backing up into pumps 22and 24, respectively. The embodiments discussed in FIGS. 6 and 7 havemany of the same components described above in connection with FIGS. 1,4 and 5. Those components are marked with the same element numbers andinclude each of the characteristics and alternatives described above forsuch numbers.

The dialysate flow path 460 is configured somewhat differently thandialysate or therapy solution flow path 60 described above. Asillustrated, heater 58 is moved in front of Pump Set 1, namely,postdilution pump 22 and predilution pump 24. Drip chamber 52 c likewisehas been moved to be in front of infusion pumps 22 and 24 of Pump Set 1.Drip chamber 52 c is provided with two temperature sensors, labeled T1and T2, as illustrated. Drip chamber 52 c also operates with vent 64 cas described above. Heated fluid leaving heater 58 enters postdilutionand predilution pumps 22 and 24.

Fluid exiting postdilution pump 22 flows via line 320 to postdilutionline 316, where that fluid enters alternative blood circuit 350 toperform convective clearance. Fluid pumped from predilution pump 24flows via predilution line 322 to drip chamber 52 a, wherein thedialysate or therapy fluid is mixed in drip chamber 52 a with bloodpumped via pump 48. The blood and dialysate or therapy fluid thereafterflow to hemofilter 312.

Assuming pumps 22 and 24 pump about the same amount of fluid over agiven period of time, fifty percent of the dialysate or therapy fluid isused for postdilution clearance, while the other fifty percent,approximately, is used for predilution clearance. It is important tonote that this ratio can be varied by changing the frequency of pumps 22and 24. The postdilution dialysate enters the patient 42 before flowingthrough hemofilter 312. The predilution dialysate or therapy fluid onthe other hand flows through hemofilter 312 before reaching patient 42.

Any of the embodiments described herein for providing dialysate, eitherprepackaged or prepared on-line, is applicable to system 310 and 410 ofFIGS. 6 and 7, as well as each of the other embodiments describedherein. Moreover, the cassette described above in connection with FIGS.2 and 3 as well as each of the embodiments shown below for configuringthe therapy machine and supply bags is additionally operable with thehemofiltration embodiments of FIGS. 6 and 7. The hemofiltration systems310 and 410 are cassette-based in one preferred embodiments and arereadily applicable to home use.

Cassette-Based Hemodiafiltration System

Referring now to FIG. 8, one embodiment of a home-basedhemodiafiltration system 510 is illustrated. Systems 10, 110 and 210described above provide a type of hemodiafiltration therapy havingconvective and diffusive transport modes caused by restriction 40 placedbetween dialyzer portions 20 and 30. System 510 on the other handprovides a hemodiafiltration system 510 via a different flowconfiguration. Nevertheless, many of the flow components ofhemodiafiltration system 510, as before, are provided on a disposablecassette, which is inserted for a single therapy into ahemodiafiltration machine.

The dialysate or therapy fluid flow path 560 of hemodiafiltration unit510 is a hybrid of the flow path 460 of system 410 described inconnection with FIG. 7 and the system 210 described in connection withFIG. 5. Like FIG. 7, a postdilution infusion pump 22 pumps dialysatedirectly into postdilution blood line 316 via line 320, whilepredilution infusion pump 24 pumps dialysate or therapy fluid via line322 into filter 20, 30. In alternative embodiments, hemodiafiltrationsystem 510 infuses dialysate only into predilution line 318 orpostdilution line 316.

Like FIG. 5, system 510 is also illustrated as having the additionalultrafiltrate pump 216 that pulls a portion of the spent dialysate fromdialyzer 20, 30 and pumps that portion through recirculation line 220and activated charcoal or other absorbent cartridge 222. As describedabove, cartridge 222 regenerates some of the spent dialysate andultrafiltrate from dialyzer 20, 30, which ultimately results in the useof less fresh fluid from containers 14 to 18 per liter of diffusiveclearance. Depending on the type of sorbent used in cartridge 222,system 210 as well as any other system described herein that usessorbents may require a sterile infusate additive 616 on line 220 toreplace electrolytes lost in the sorbent cartridge and a conductivitytemperature sensor 62, 63 to measure the electrolytes independently ofthe infusion. It should appreciated, however, that hemodiafiltrationsystem 510 does not require a regeneration loop 220 or cartridge 224.

Hemodiafiltration system 510 operates in a similar manner to the system10, 110 and 210 described above. That is, both systems provideconvective and diffusive clearance modes. In system 510, the convectiveclearance occurs because lines 320 and 322 from the infusion pumpsconvey dialysate or therapy fluid directly into the blood circuit 350.Check valves 326 are placed in both lines 320 and 322 to prevent bloodfrom backing up into pumps 22 and 24, respectively. Diffusive clearancealso occurs because dialysate is additionally moved across the membranesinside dialyzer 20, 30.

At least a portion of many of the sensors, the pump chambers, the fluidheating pathway, the fluid flow portions of valves 56 as well as manyother components of system 510 are provided in whole or in part on acassette, such as cassette 100 a. Cassette 100 a is then loaded into ahemodiafiltration machine for a single use and then discarded. System510 is thereby well suited for home use.

Recirculation

The systems described previously require a fluid source, such as,sterile dialysate from bags, e.g., as in FIG. 1, or from a fluidgeneration pack, e.g., as seen in FIG. 2. FIGS. 9 to 11 describe systemsthat are applicable to any of the therapies described herein (e.g.,using convection and/or diffusive clearance modes). The systems of FIGS.9 to 11, however, use a recirculating sorbent system with variousfilters to produce an ultrapure dialysate source.

Referring now to FIGS. 9 to 11, various sorbent-based regenerationsystems are illustrated. FIG. 9 shows a sorbent-based regenerationsystem 610 that performs the back-filtered convection and diffusiondescribed in systems 10, 110 and 210 above. FIG. 10 shows the system(610 of FIG. 9 or 710 of FIG. 11) being shunted at start-up for rinsingand priming. System 710 of FIG. 11 is a hemofiltration system usingsorbent-based regeneration, which is applicable to pre- and postdilutiontype HF systems as well as the HDF system 510 described in FIG. 8.

In the system 610 of FIG. 9, patient 42 uses an initial five liter bagof sterile dialysate, which is installed in a rigid container to form areservoir 612. Alternatively, five liters of water and concentratepowders or liquids are mixed inside reservoir 612 to form an initialtherapy solution.

FIG. 10 illustrates that a shunt 614 is placed across dialyzers 20 and30 at the beginning of treatment. A sorbent cartridge 222 is placed inthe dialysate flow path 620 downstream of shunt 614. Cartridge 222 is,for example, any of the types of sorbent systems described above inconnection with system 210 of FIG. 5. An infusate 616 including, e.g.,calcium, magnesium and/or potassium is pumped via infusate pump 618 intoreservoir 612 as necessary to replenish ions that are removed via thesorbent cartridge 222.

Heater 58 heats the solution leaving reservoir 612. After the solutionis heated, system 610 prompts the user or patient 42 to install adisposable, sterile cassette, such as cassette 100 a described above. Atleast a portion of the air bubble detectors 54, heating elements ofheater 58, pressure sensors 46, temperature sensors 62, etc., areintegrated into the cassette in both the dialysate and extracorporealblood flow paths as necessary to allow for a safe treatment for thepatient and reliable operation of system 610. The blood circuit 50 isprimed with a saline bag connected to the arterial bloodline or viabackfiltering dialysate or saline through venous dialyzer 20.

The patient is connected to the arterial and venous access lines 44 aand 44 b respectively, and treatment begins. For short therapies, thedialysate flow can be relatively high, such as three hundred ml/min forthree hours or one hundred ml/min for up to eight hours. Dialysate pumps22 and 24 and UF pumps 26 and 28 control flow to and from dialyzers 20and 30. By increasing the pumping rate of pumps 26 and 28 that removethe effluent dialysate from arterial dialyzer 30, the fluid accumulatedin the patient in the interdialytic period is removed. The fluid flowportions of dialysate/UF pumps 22 to 28 are integrated into the cassettealong with the extracorporeal circuit in one embodiment. Alternatively,those components are maintained separately from the cassette and areintegrated into the machine.

FIG. 9 shows two volumetric devices 22 and 24 for dialysate flow and twofor 26 and 28. Alternatively, one pump is employed on the input and oneon the output, however, such configuration could create pulsitile flow,which is less desirable.

Fresh dialysate flows initially to venous hemodialyzer 20. A restriction40 placed between dialyzers 20 and 30 builds backpressure in dialyzer20, so that a relatively large amount of the dialysate is backfilteredinto blood circuit 50, with the remaining portion of the dialysateflowing to arterial dialyzer 30. System 610 in that manner providesdiffusive as well as convective clearance as has been described herein.

Used dialysate and UF pulled from arterial dialyzer 30 is thencirculated through the sorbent cartridge 222. Cartridge 222 removeswaste products from the spent dialysate/UF fluid. The cleaned fluid ispumped to reservoir/bag 612, where infusate 616 is added to replace theelectrolytes removed by the sorbent cartridge 222.

The majority of dialysate flow path 620 is located within the cassette.The cassette is single use in one embodiment but is alternativelyreusable with suitable disinfection and/or sterilization. Most allcomponents of the extracorporeal circuit 50 may be integrated into thecassette except, e.g., the tubing extending to and from the patient. Theextracorporeal circuit 50 of system 610 is similar to the circuit 50described above in systems 10, 110 and 210.

The dialysate/infusate is heated as it exits reservoir 612 and flowspast a temperature/conductivity sensor 62. If the solution is too hot,too cold or otherwise outside of a defined physiological range, a bypassvalve 56 provided with ultrafilter 626 is closed and a purge valve 56 inbypass line 628 is opened to bypass dialyzers 20 and 30. During thatbypass, both the infusate and UF pumps 22 to 28 may be stopped. Tofacilitate the bypass and a smooth, steady flow of fluid to/fromreservoir 612, a second circulation pump 624 b may be employed.

When the solution is within the defined temperature/physiological range,the solution passes through reusable ultrafilter 626, which employs amolecular weight cutoff that filters bacteria. Ultrafilter 626 alsofilters and absorbs endotoxin. The filtration of system 610, includingultrafilter 626, is intended to provide dialysate in as pure a form aspossible. Ultrafilter 626 may also be a microfilter, if the microfiltercan remove acceptable amounts of bacteria and pyrogens.

From ultrafilter 626 the dialysate or therapy solution is pumped toinfusion pumps 22 and 24. Flow measuring devices 32 to 38 monitor thevolume of the fluid pumped by pumps 22 to 28. Pumps 22 to 28 areconfigured as described above to leak to an external point. Any leaksare diverted into a moisture sensor built into the cassette and/orcassette/machine interface, so that corrective action is taken upondetection of a leak.

Fluid flows from infusion pumps 22 and 24 through a small 0.2 micronmicrofilter 630 in one embodiment. Filter 630 is integrated into thecassette and provides additional filtration of bacteria and endotoxin.The dialysate flows from filter 630 to venous dialyzer 20, which employshigh flux membranes. The dialysate flow path 620 connects the venous andarterial dialyzers via a restriction 40 between the two dialyzers.Restriction 40 provides backpressure to drive a significant amount ofthe dialysate directly into the blood circuit 50 inside venous dialyzer20. The remainder of the dialysate flows to arterial dialyzer 30.

UF pumps 26 and 28 are provided on the exit side of the arterialdialyzer 30. Those pumps are normally configured to pump at the rate ofthe fresh dialysate plus an additional amount to remove the fluidaccumulated in the patient between treatment sessions. The useddialysate fluid and UF fluid is then circulated to the sorbent cartridge222 and cleaned before returning to reservoir 612 and receiving aninfusate 616 of e.g., calcium chloride, magnesium chloride, potassiumchloride and possibly sodium acetate. As described above in connectionwith system 10, pumps 22 to 28 may operate differently for priming, forbolus infusion or for blood rinseback.

FIG. 11 illustrates a system 710, which replaces dialyzers 20 and 30with a hemofilter 312. System 710 is configurable to providepredilution, postdilution or both types of HF therapies via valves 56and pre and postdilution flow lines 712 and 714, respectively. Pre andpost dilution HF eliminates the need for an anti-coagulant. System 710can employ multiple ultrafilters 626 and multiple bypass lines 628 asillustrated for redundancy. Multiple filters in series ensure that ifone filter becomes compromised or otherwise does not function properly,the other filter in the series ensures proper filtration. The filterseach have a rated log reduction of bacteria and endotoxin. Thus, ifbacteria levels reach a high enough point, some bacteria could becarried through the first filter in a series to the second filter in theseries, and so on.

Systems 610 and 710 include a number of alternative embodiments.Ultrafilters 626 and/or microfilter 630 may or may not be reusable.Pumps 22 to 28 and flow measuring devices 32 to 38 include any of thealternatives described above in connection with system 10, such as thematched flow equalizers in such as in the System 1000™, produced by theassignee of the present invention. Any of the alternatives may be atleast partially integrated with the cassette or provided elsewhere inthe dialysis machine. A further alternative method is to use othervolumetric pumping technology, such as piston pumps (with some pistonpumps, depending upon if the piston exposes the solution to air, theultrafilter needs to be placed after the pumps in the fresh dialysateloop to prevent the solution from becoming contaminated). Still further,flow monitoring could be employed instead of the volumetric pumps. Here,flow sensors measure flow and provide flowrate feedback to one or morepumps located upstream and/or downstream of the dialyzers 20, 30 orhemofilter 312.

Systems Using Peristaltic Pumping

Referring now to systems 810 and 910 of FIGS. 12 and 13, respectively,alternative medical fluid treatment systems using peristaltic pumps 820and 830 to pump the dialysate fluid from bags 14, 16 and 18 andultrafiltrate from a blood filter are illustrated. FIGS. 12 and 13 aresimplified with respect to the figures illustrating earlier systems. Itshould be appreciated that many of the components and devices shownabove in those systems are also used in systems 810 and 910 asappropriate. It is unnecessary to repeat the inclusion of each of thosecomponents and devices in FIGS. 12 and 13. Moreover, elements in FIGS.12 and 13 listed with like element numbers with respect to those shownabove operate the same as described above and include each of thealternatives for those element numbers described above.

System 810 of FIG. 12 illustrates a hemodiafiltration system usinginline hemodialyzers 20 and 30, separated by restriction 40, asdescribed above. Blood flows from arterial access line 44 a ofextracorporeal circuit 50 via peristaltic pump 48, through arterialdialyzer 30, through venous dialyzer 20, into venous drip chamber 52 b,through blood leak detector 54 and clamp or valve 56 and venous accessline 44 b back into patient 42. Dialysate flows from one of the sourcebags 14, 16 or 18 through drip chamber 52 c and past heater 58. Insystem 810, peristaltic pumps 820 and 830 are used to drive thedialysate or therapy fluid from the source bags to venous dialyzer 20.

Valves 56 a to 56 h are configured and arranged to enable eitherperistaltic pump 820 or peristaltic pump 830 to perform either of thefluid infusion or fluid removal tasks, namely, to infuse fluid intovenous dialyzer 20 or to pull ultrafiltrate from arterial dialyzer 30.Peristaltic pumps are inherently less accurate than the volumetricdiaphragm pumps described above as well as other types of pumps orvolumetric devices, such as fluid balancing chambers. Due to thisinaccuracy, peristaltic pumps may have to be combined with a balancescale or another balancing method. Peristaltic pumps are, however, easyto sterilize and maintain in an injectible quality state, the pumps aregenerally hearty, robust and also provide built-in clamping when thepump stops pumping because the pump head pinches closed the tubingwrapped around the head. The pumps are also well accepted by thedialysis community. The valve arrangement of valves 56 a to 56 h and theuse of the peristaltic pumps is advantageous for the above reasons.

The inaccuracy inherent in peristaltic pumps is repeatable especiallywhen the pumps are rotated in the same direction. Systems 810 and 910provide dual pumps 820 and 830 and valves 56 a to 56 h that are openedand closed to enable the same pump 820 and 830 to be rotated in the samedirection for the same number of pump-in strokes and pump-out strokes.That feature cancels most error associated with the pumps. The pumpsthen perform additional pump out strokes to remove the desired amount ofultrafiltrate.

It should be appreciated that the above canceling can also be achievedby running one pump in one direction for the appropriate number ofstrokes and alternating the valves to sequentially pump-in and pump-outwith the single peristaltic pump. Such an arrangement creates pulsitileflow, however, which is less desirable than a steady flow from dualpumps 820 and 830. Therapy time is reduced as are the chances ofhemoconcentrating the patient.

Valves 56 a and 56 b enable dialysate heated by heater 58 to flow toeither peristaltic pump 820 or 830. Valves 56 c and 56 d in turn enablefluid to flow from either pump 820 or 830 to venous dialyzer 20. Valves56 e and 56 f enable ultrafiltrate to be pulled from arterial dialyzer30 to either peristaltic pump 820 or 830, respectively. In turn, valves56 g and 56 h enable the ultrafiltrate pulled from dialyzer 30 to bepumped via either valve 820 or 830, respectively, to drain bag 12, 14 or16.

The operation of dialyzers 20 and 30 in combination with restriction 40does not change in system 810 from their operation described above inconnection with system 10 of FIG. 1. The dual operating pumps 820 and830 enable a continuous flow of fluid into and out of dialyzers 20 and30. Importantly, as with the membrane pumps 22 to 28 described above,the tubing used with peristaltic pumps 820 and 830 can be sterilizedwith methods such as gamma, ebeam or ethylene oxide, and operatedwithout compromising such sterilization.

Flow or volume measuring devices 840 and 850 are each provided tooperate with a respective pump 820 or 830, respectively. Devices 840 and850 can provide tachometer feedback, for example, measuring the speed ofrotation of the peristaltic pump head in one example. In anotherexample, measuring devices 840 and 850 count to the number of strokesmade by the head of peristaltic pumps 820 and 830. In a furtheralternative embodiment, ultrasonic, mass flow, vortex shedding, or othertype of flow measurement technique is used to measure the amount offluid entering or exiting pumps 820 and 830. Various embodiments showingperistaltic pumps in combination with one or more balancing chamber orvolumetric control device are illustrated in detail below.

System 910 of FIG. 13 illustrates a hemofiltration version of system 810described in FIG. 12. System 910 is similar in all respects to system810 except that hemofilter 312 replaces hemodialyzers 20 and 30 andrestriction 40 of system 810. Also, the inlet line 314 extending fromvalves 56 c and 56 d is connected to line 824 extending from hemofilter312 to venous drip chamber 52 b in system 910. In system 810 of FIG. 12,line 314 as illustrated is connected instead to the inlet of venousdialyzer 20. Line 328 in both systems 810 and 910 exits the relevantblood filtering device and flows to valves 56 e or 56 f. Thus, thefunctioning of valves 56 a to 56 h does not change from system 810 tosystem 910. That is, valves 56 a and 56 b operate as inlet dialysate orsubstitution valves in both systems. Valves 56 c and 56 d operate asoutlet dialysate valves in both systems. Valves 56 e and 56 f operate asultrafiltrate inlet valves in both systems. Valves 56 g and 56 h bothoperate as ultrafiltrate outlet valves in both systems. System 910optionally provides a bypass line 828 and shunt valve 56 i that enablessystem 910 to perform pre or postdilution hemofiltration as describedabove.

Any of the alternative embodiments for providing a sterile solution orfor regenerating used solution described above are applicable to systems810 and 910. Further, each of the components described above, such asvalves 56, drip chambers 52 (collectively referring to drip chambers 52a, 52 b and 52 c), heater 58, etc., or those portions thereof thatcontact the fluids used in the systems, can be provided in a disposablecassette in systems 810 and 910. In particular, shown below are machinesthat house the flow devices as well as the disposable cassette. Thosemachines show that a majority of the peristaltic blood pump is locatedwithin the machine, with the peristaltic pump head located outside ofthe machine. Such arrangement is applicable to systems 810 and 910,which use multiple peristaltic pumps. The cassette can have multipletubing portions that the patient or operator wraps around the externallylocated peristaltic pump heads for use.

Co-Current Flow

Referring now to system 950 of FIG. 14, an alternative medical fluidtreatment system using co-current flow is illustrated. System 950 ofFIG. 14 includes many of the same components described above, forexample, in connection with system 10 of FIG. 1. Many element numbersshown in FIG. 14 are the same as the element numbers shown in previousembodiments. Those like element numbers in FIG. 14 operate the same asdescribed above for those numbers and include each of the alternativesdescribed previously for same.

System 950 operates in a similar manner to system 10 of FIG. 1, both ofwhich include dual dialyzers 20 and 30, and a restriction, such asvariable restriction 40, placed between the dialyzer portions. System 10of FIG. 1, it should be appreciated, is a counter-current flow system.That is, dialysate line 314 in FIG. 1, which receives therapy fluid frompumps 22 and 24, in turn feeds the therapy fluid into venous dialyzer20. The fluid flows through venous dialyzer 20, variable restriction 40and through arterial dialyzer 30. At the same time, blood flowsinitially into arterial dialyzer 30, continues through blood circuit 50,through venous dialyzer 20 and eventually into patient 42. System 950 ofFIG. 14, on the other hand, includes output dialysate line 952 insteadof line 314 in FIG. 1. Dialysate line 952 carries fresh and heatedtherapy fluid into arterial dialyzer 30 instead of venous dialyzer 20.The dialysate in system 950 therefore flows from arterial dialyzer 30,through variable restriction 40, into venous dialyzer 20 and out venousdialyzer 20 to ultrafiltrate pumps 26 and 28. Blood leak detector 66 isalternatively placed upstream of pumps 26 and 28 as illustrated in FIG.14 or downstream of those pumps as illustrated in FIG. 1.

Co-current flow of dialysate via line 952 of system 950 is beneficial inone respect because, as with predilution hemofiltration, dialysate isintroduced into arterial dialyzer 30 at the start of the bloodfiltration portion of blood circuit 50, and may, therefore, help toprevent hemoconcentration of the patient's blood. Variable restriction40 operates to backfilter therapy fluid inside arterial dialyzer 30 intoextracorporeal circuit 50. Afterwards, blood and therapy fluid flow intovenous dialyzer 20 via bloodline 50 and are subjected to diffusiveclearance via the non-backfiltered dialysate that flows from arterialdialyzer 30 into venous dialyzer 20 through restriction 40. The roles ofdialyzers 20 and 30 are reversed in system 950 with respect to system 10of FIG. 1, wherein the clearance mode in venous dialyzer 20 is primarilydiffusive, while the clearance mode in arterial dialyzer 30 is primarilyconvective.

Operation of system 950 is otherwise substantially similar to thatdescribed above in connection with system 10 of FIG. 1. While system 950is operable with supply bags 14 to 18 and drain bag 12, any of theabove-described embodiments for supplying fresh dialysate arealternatively operable with system 950. Further, system 950 is operablewith the regeneration sorbent system described above in connection withsystem 210 of FIG. 5. Still further, co-current flow can be provided inconnection with the hemodiafiltration system 510 of FIG. 8. Stillfurther, the volumetric diaphragm pumps 22 to 28 can be replaced byperistaltic pumps 820 and 830, in accordance with the teachingsdescribed above in connection with system 810 of FIG. 12.

Ultrafiltrate Control Boyle's Law

Referring now to FIGS. 15 and 16, a method of determining the volume offluid pumped through a membrane pump is illustrated. Pumps 22 and 24described above are shown for example. As discussed herein, pumps 22 and24 include pump chambers defined at least partially by a rigid cassette,such as cassette 100 a. The cassette includes a flexible membrane orsheeting. Another portion of the pump chamber is defined in oneembodiment by the renal replacement therapy machine into which thecassette is inserted. In FIGS. 15 and 16, pump 22 includes a membrane252. Pump 24 includes a membrane 254. Positive and negative tanks 268and 270 move membranes 252 and 254 to pump fluid via positive andnegative pressure via valves 274, 276, 278 and 280 as needed. Thepneumatic system also includes reference reservoirs 256 and 258.Reservoir 256 communicates with air residing on the non-fluid side ofmembrane 252 of pump 22. Likewise, reference reservoir 258 communicateswith air residing on the non-fluid side of membrane 254 of pump 24.

Reference reservoirs 256 and 258 have a constant and known volume. Inthe equations shown below the volumes of reservoirs 256 and 258 aredesignated as V1 reservoir and V2 reservoir. In the example, the volumesof pressure sensors that measure V1 reservoir and V2 reservoir are 20ml. The blood therapy treatment unit also has pressure sensors thatmeasure the pressure inside reference reservoirs 256 and 258. In FIG.15, when valves 260 and 262 are closed and vent valves 264 and 266leading to sound absorbers 286 and 288 are open, the pressure insidereservoirs 256 or 258 reaches atmospheric pressure or approximately 15psia. In FIG. 16, when vent valves 264 and 266 are closed and reservoirvalves 260 and 262 are opened, the pressure inside pump chamber 1equalizes with the pressure inside reservoir 256. The pressure insidepump chamber 2 equalizes with the pressure inside reservoir 258.

The cassette is also configured such that a pressure sensor housedwithin the blood therapy unit measures the initial and final air fluidpressures, inside pumps 22 and 24. In the equations shown below, thefluid pressure inside pump 22 is designated as P1 chamber. The fluidpressure inside pump 24 is designated as P2 chamber. The fluid pressuresvary from an initial pressure to a final pressure. Likewise, thepressures P1 and P2 within reservoirs 256 and 258 designated as P1 andP2 reservoir, respectively, vary from an initial pressure to a finalpressure.

The volume of air within either one of the pumps 22 or 24 (volume V1 forpump 22 which is supposed to be full is shown for example) is calculatedvia Equation 1 as follows:

$\begin{matrix}{{V\; 1\mspace{14mu}\left( {{air},{{full}\mspace{14mu}{chamber}}} \right)} = {\frac{\left( {{P\; 1\mspace{14mu}{reservoir}},{initial}} \right) - \left( {{P\mspace{11mu} 1\mspace{14mu}{reservoir}},{final}} \right)}{\left( {{P\; 1\mspace{14mu}{chamber}},{final}} \right) - \left( {{P\mspace{11mu} 1\mspace{14mu}{chamber}},{initial}} \right)} \times V\; 1\mspace{14mu}({reservoir})}} & {{EQUATION}\mspace{14mu} 1}\end{matrix}$

The volume of air for an empty chamber for either one of the pumps 22 or24 (shown in this example for pump 24 or V2) is calculated according toEquation 2 as follows:

$\begin{matrix}{{V\; 2\mspace{14mu}\left( {{air},{{empty}\mspace{14mu}{chamber}}} \right)} = {\frac{\left( {{P\; 2\mspace{14mu}{reservoir}},{initial}} \right) - \left( {{P\; 2\mspace{14mu}{reservoir}},{final}} \right)}{\left( {{P\; 2\mspace{14mu}{chamber}},{final}} \right) - \left( {{P\; 2\mspace{14mu}{chamber}},{initial}} \right)} \times V\; 2\mspace{14mu}({reservoir})}} & {{EQUATION}\mspace{14mu} 2}\end{matrix}$

Each of the pressures for each of the pumps 22 and 24 shown in Equation1 is measured via a suitably placed transducer. The final air pressurewithin the reservoirs 256 and 258 is also measured. The final pressureof air within the chambers, which should equal the final reservoirpressure can be double checked. The measured pressures satisfy thenumerators and denominators in Equations 1 and 2. As discussed above,the volumes of the reservoirs V1 and V2 are constant and known.

For each pump then, Equation 3 calculates the volume pumped for a strokeas follows:

$\begin{matrix}{{{Volume}\mspace{14mu}{fluid}\mspace{14mu}{pumped}\mspace{14mu}{for}\mspace{14mu}{pump}\mspace{14mu} 1\mspace{14mu}{or}\mspace{14mu} 2} = {{V\; 1\mspace{14mu}{or}\mspace{14mu} V\; 2\mspace{14mu}\left( {{air},{{empty}\mspace{14mu}{chamber}}} \right)} - {V\; 1\mspace{14mu}{or}\mspace{14mu} V\; 2\mspace{14mu}\left( {{air},{{full}\mspace{14mu}{chamber}}} \right)}}} & {{EQUATION}\mspace{14mu} 3}\end{matrix}$

The fluid volume pumped for a stroke of a pump is equal to the volume ofair when that pump chamber is empty or void of fluid less the volume ofair in that pump chamber when the chamber is expected to be full offluid. It should be appreciated that the Equations 1 to 3 that arederived from Boyle's law compensate for air bubbles that may be presentin the dialysate and for instances where membranes 252 and 254 may nottravel fully to one side or the other of the pump chambers of pumps 22and 24, respectively.

The above-described method provides an accurate, after-the-fact,measurement of the volume of fluid that has been moved by either one ofthe pumps 22 and 24. By using the volumetrically controlled pumps, anexact amount of fluid can be exchanged with the patient and an exactamount of ultrafiltrate can be removed from the patient by setting thefluid removal pumps, e.g., pumps 26 and 28, to pump faster or morevolume than the fluid inlet pumps 22 and 24 (see for example, in FIGS.1, 4, 6, 7). Because the volume for each stroke can be calculated, theamount of fluid removed from the patient can be summed and controlled.

It should be appreciated that Equations 1 to 3 described above could beused in a machine that mechanically moves membranes 252 and 254. In suchcase, positive and negative pressure tanks 268 and 270 would not beneeded, however, separate reference reservoirs 256 and 258 as well as atest pressure tank 272 are needed. Test pressure tank 272 may beemployed even in the present embodiment so that pressure tanks 268 and270 may be operated independent from the volume control.

Calculating the volume of fluid pumped according to Equations 1 to 3provides information on how much volume has been moved per pump stroke.The equations do not provide real time information of actual fluid flow.That is the valve opening and closing, sequence in FIGS. 15 and 16occurs between pump strokes, when valves 274, 276, 278 and 280 areclosed, isolating the pumps from the positive and negative pressuresources. When the pumps are pumping fluid, reference reservoirs 256 and258 are isolated from the pump.

If fluid flow stops or occurs at a flow rate that is greater than adesired flow rate, the pneumatic system may not detect this until afterthe undesired fluid flow rate has occurred. In blood therapy systems,such as dialysis, hemofiltration or hemodiafiltration, if the withdrawalof the fluid from circulating blood exceeds about thirty percent of theblood flow rate, the blood thickens and may clog the dialyzer orhemofilter fibers. If the dialyzer or filter becomes clogged, therapymay have to be terminated and the patient may lose an amount of bloodtrapped in the extracorporeal circuit.

The apparatus shown in FIGS. 15 and 16, however, provides a solution forreal-time flow rate data for both blood flow and dialysate infusion andremoval. The real-time flow rate is again calculated using principals ofBoyle's law. As described above, equations one and two calculate thevolume of air within the pump chambers 22 and 24 when those chambers areeither full or empty. In this method, valves 260 and 262 to referencereservoirs 256 and 258 are closed and the appropriate valves to positivepressure tank 268 and negative pressure tank 270 are opened. Forexample, valve 274 may be opened to supply positive pressure to pump 22to push fluid from that pump. At the same time, valve 280 may be openedto pull a vacuum on pump 24 to draw fluid into the pump. Since thevolumes of air in the pump chambers are known from Equations 1 and 2,those volumes are added to the known volumes of air in pressurereservoirs 268 and 270 (e.g., 500 ml) to form total initial volumes. Thepressures are measured as the membranes 252 and 254 move due to thesupplied pressures. The change in pressure over time corresponds to achange in volume one time, which yields a flowrate.

In the following equations, the total initial volume in pump 22 and therespective pressure chamber is V1 total, initial=V1 chamber, initialplus V_(pos/neg) tank. The total volume in pump 24 and the respectivepressure chamber is V2 total, initial=V2 chamber, initial plusV_(pos/neg) tank. The pressure of the pump 22 system as measured at thepositive or negative tank is initially P_(pos/neg), tank, initial. Thepressure of the pump 24 system as measured at the positive or negativetank is initially P_(pos/neg) tank, initial. The pressure of eithersystem at any time T is P_(pos/neg) tank, time T. The volume in eitherpump at time T is therefore as follows:

$\begin{matrix}{{V\; 1\mspace{14mu}{or}\mspace{14mu} V\; 2\mspace{14mu}{total}},{{{time}\mspace{14mu} T} = {\frac{{P_{{pos}/{neg}}\mspace{14mu}{tank}},{initial}}{{P_{{pos}/{neg}}\mspace{14mu}{tank}},{{time}\mspace{14mu} T}}*V\; 1\mspace{14mu}{or}\mspace{14mu} V\; 2\mspace{14mu}{total}}},{initial}} & {{EQUATION}\mspace{14mu} 4}\end{matrix}$

The fluid moved by either pump at time T is therefore as follows:V _(fluid) moved by pump 1 or 2=V1 or V2 total,time T−V1 or V2total,initial  EQUATION 5

Knowing the time T and the volume of fluid moved by pump 22 or 24 attime T, the flow rate on a real time basis may be calculated, displayedand used to control the renal failure therapy systems of the presentinvention.

Ultrafiltrate Control Single Balance Chamber

Each of the systems 10, 110, 210, 310, 410, 510, 610, 710 and 950 thatemploy membrane pumps, such as pumps 22, 24, 26 and 28 are capable ofmetering out precise amounts of fluid, which can be controlled asdescribed above for example via Boyle's Law. For manufacturing and costreasons, however, it may be desirable to use a different type of pump tomove spent and effluent dialysate. For example, peristaltic pumps, suchas the blood pump 48 described above, may more easily integrate into adisposable cassette or tubing set because the disposable part of aperistaltic pump is essentially a loop of tubing. The accuracy ofperistaltic pumps, however, may not alone be precise enough for pumpingdialysate in systems, such as hemofiltration, hemodialysis andhemodiafiltration, in which a prescribed amount of ultrafiltrate oreffluent dialysate needs to be removed from the patient.

Patient 42 between dialysis or hemofiltration treatments gains waterdepending on the extent of kidney loss and fluid intake. Many peoplesuffering kidney failure do not have the ability to urinate. Over thetime between dialysis treatments, those patients accumulate fluid. Thepatient's total fluid weight gain can vary over different treatmentsbased on the amount of fluid the patient has consumed between treatmentsand the amount of time between treatments. Therefore, the systems andmethods of the present invention need to have a controllable andaccurate way of removing whatever amount of fluid is needed to be takenfrom the patient during the home treatment. Because home patients cantreat themselves more often, the amount of fluid that needs to beremoved will be typically less than that for in-center treatments.Nevertheless, the home dialysis machine needs to be able to remove theamount of fluid gained between treatments.

Referring now to FIGS. 17 to 22, various systems 300 a to 300 f(referred to herein collectively as systems 300 or generally as system300) employing a single balance chamber 340 are illustrated. Systems 300a, 300 b, 300 c, 300 d, and 300 e each operate with a peristalticdialysate pump 370. As discussed above, a peristaltic pump is desirablefor a cassette-based system because the cassette portion of the pumpconsists primarily of a looped tube that fits around the pumping headhoused by the renal failure therapy machine.

Balancing chamber 340 provides the level of volumetric accuracy providedby the membrane pumps discussed above. The majority of systems 300 useperistaltic pump 370 to drive the dialysate, while balancing chamber 340meters a precise amount of dialysate to the dialyzer, hemofiltrationline, etc. Balance chamber 340 in turn meters a pressurized amount ofultrafiltrate from the dialyzer or hemofilter. System 300 f of FIG. 22shows one alternative embodiment, which combines balance chamber 340with one of the fresh dialysate membrane pumps 22 or 24 and one of theeffluent dialysate membrane pumps 26 or 28 discussed above.

One primary difference between systems 300 a to 300 d is the modality ortype of therapy with which balance chamber 340 and peristaltic dialysatepump 370 are used. System 300 a of FIG. 17 uses a single dialyzer 20 or30. In system 300 a, the modality performed is a primarily diffusivehemodialysis treatment unless the dialyzer has an internal restrictionas mentioned previously. However this dialyzer requires a high fluxmembrane. Longer and narrower dialyzers will increase the percentage ofbackfiltration. Also a dialyzer having an internal flow restrictionsuitable for use, such as described in commonly owned U.S. Pat. No.5,730,712, entitled “Extracorporeal Blood Treatment Apparatus andMethod”, is incorporated herein by reference. That dialyzer as indicatedis limited to having a fixed orifice. The modality or therapy of system300 b of FIG. 18 is the advanced convection hemodialysis (“ECHD”)treatment provided by arterial and venous high flux dialyzers 20 and 30,respectively, which are separated by variable restriction 40. Themodality or treatment provided by system 300 c of FIG. 19 is theconvective treatment, hemofiltration, wherein substitution fluid ispumped directly into venous line 44 b, and wherein ultrafiltrate isremoved via a hemofilter 312.

System 300 d of FIG. 20 illustrates balance chamber 340 operating incombination with a hemodiafiltration modality. As discussed above,hemodiafiltration combines the diffusive clearance of hemodialysis withthe convective clearance of hemofiltration. As seen in FIG. 20, adialyzer 20 or 30 is provided. Also, a separate line 320, coupled withan additional peristaltic pump 380, feeds dialysate or substitutionfluid directly into venous line 44 b. FIGS. 17 to 20 illustrate that thevolumetric control of ultrafiltration via single balance chamber 340 canbe provided for many different types of modalities, such ashemodialysis, ECHD, hemofiltration and hemodiafiltration. The remainderof the description may in certain cases be specific to dialysis or ECHD.It should be appreciated, however, that those teachings are applicableto each of the systems 300 shown in FIGS. 17 to 20.

Viewing any of the systems 300, effluent or spent dialysate flows from adialyzer 20, 30 or hemofilter 312 through effluent line 328 and valve V5to peristaltic dialysate pump 370. While pump 370 in one preferredembodiment is a peristaltic pump, pump 370 can alternatively be of anydesired variety, such as a piston-driven diaphragm pump, a pneumaticpump or a gear pump. The output of fluid from pump 370 flows via valveV4 to a spent side 342 of the balance chamber 340. Similar to theflexible membrane in the membrane pump, balance chamber 340 is separatedinto a spent compartment 342 and a fresh compartment 344 via a flexiblemembrane 346. As discussed herein, valves 56, such as valve V4, may beany suitable type of valve, such as a standard solenoid valve or avolcano-type valve formed partially in the cassette, which is the sameor similar to that used in a HomeChoice® system.

Balance chamber 340 is a passive volumetric metering device. The same orsubstantially the same amount of fluid is pushed out of balance chamber340 as is received into balance chamber 340. Pumping effluent dialysateinto spent compartment 342 in turn pushes membrane 346, which forces anequal amount of fresh dialysate to exit fresh compartment 344 and travelthrough valve V1 in line 314 and into dialyzer 20, 30 or into venousline 44 b depending on the modality used. FIGS. 17 to 20 are not meantto describe each of the flow components that would be associated withthe respective system 300. For example, if balance chamber 340 pushessubstitution fluid through valve V1 and inlet line 314, a suitable checkvalve would be placed in line 314, which would prevent blood frombacking into balance chamber 340. When enough effluent dialysate entersspent chamber 342 via valve V4, so that membrane 346 traverses all theway or substantially all the way towards the chamber wall of freshcompartment 344, valves V1, V4 and V5 shut off.

FIGS. 17 to 20 show a pressure relief 332 located between the inlet andoutlet of dialysate pump 370. In one embodiment, pressure relief 332includes a check valve that cracks or relieves at a specific pressure.Alternatively, pressure relief 332 includes a valve seat that relievespressure at a preset value. For example, a spring tension can controlthe amount of force or pressure within the pressure relief line that isneeded to crack or open pressure relief 332. When system 300 is usedwith a disposable cassette, the opening of the valve or seat isconfigured so that the relieved dialysate is collected and does notcontact any of the components within the renal failure therapy machine.

In an alternative embodiment, dialysate pump 370 is placed upstream ofheater 58. In such case, pressure relief 332 can extend from the inletof dialysate pump 370 to fresh dialysate inlet line 334 upstream ofvalve V3. In yet another alternative embodiment, pressure relief 332incorporates sterile dialysate bags or substitution bags 14 to 18. Thatconfiguration is desirable because it prevents inline heater 58 fromoverheating fluid when idle, e.g., during an ultrafiltration stroke.

A cycle in which effluent fluid is removed from the dialyzer orhemofilter and fresh fluid is sent to the patient or dialyzer has beendescribed. A next cycle sends fluid to drain. Here, heated and freshdialysate from one of supplies 14, 16 or 18 flows through valve V6,dialysate pump 370, valve V3 and into dialysate compartment 344 ofbalance chamber 340. Valves V1, V4 and V5 are closed. The receipt offresh dialysate into compartment 344 pushes flexible membrane 346,causing an equal amount of spent or effluent dialysate to drain viavalve V2 and drain line 338. Depending on the point in time in thetherapy in which this drain cycle takes place, spent effluent can besent to drain bag 12 or one of the used supply bags 14 or 16. Once allof the spent dialysate in chamber 342 is emptied through valve V2 anddrain line 338, all valves V1 to V6 are shut off. The fill with spentfluid and pump to patient cycle may then be repeated via the cycledescribed above.

It should be appreciated that the two cycles just described ensure thatan equal amount of fluid is sent to the patient and taken from thepatient. A UF sequence is described below in which fluid is taken fromthe patient but not sent to the patient. Calculating the total volume ofultrafiltrate moved is readily done in the illustrated systems 300. Thecumulative volume of the UF cycles is added to determine the totalamount of fluid removed from the patient.

In one embodiment, pump 370 is run at a slower speed when freshdialysate is pumped to the dialyzer or patient than when dialysate ispumped from the patient. The difference in speed increases the time thatfresh dialysate is flowing to the dialyzer. For hemodialysis, the speeddifference increases the diffusion time by increasing the time thatdialysate is flowing along the hollow fibers within the dialyzer. Theincreased time also benefits HF, HDF and ECHD by producing a moregradual ultrafiltration of the patient. The gradual ultrafiltrationreduces the risk of hemoconcentration.

To remove ultrafiltrate, system 300 begins from an all valves closedposition and opens valves V2, V3 and V5. Pump 370 causes effluentdialysate to fill the fresh compartment 344 with spent dialysate. Thataction moves membrane 346 and forces an equal amount of spent fluidpreviously removed from the patient in spent chamber 342 to be pushedthrough valve V2 and line 338 to one of the drain bags. Because thesource of fluid used to push this amount of fluid to drain is useddialysate, the amount of used dialysate pumped into fresh compartment344 is also removed from the patient as ultrafiltrate. That is, there isa small net loss of fluid from the patient during this cycle. In oneembodiment, the ultrafiltrate cycle just described is timed to occurevery so often during the previously described pump to patient and pumpto drain cycles, so as to remove an overall net amount of ultrafiltratethat has collected in the patient between treatments. That net amount isentered into the machine at the start of therapy.

One potential drawback of the single balance chamber 340 and singledialysate pump 370 approach is that when spent dialysate is pulled fromthe dialyzer or hemofilter through line 328 and line 336 via pump 370into the spent chamber or compartment 342, a small amount of freshdialysate is also pushed into spent compartment 342. That small amountof fresh dialysate is the amount that remains in the tubing leading fromvalve V6, bending around peristaltic pump 370, and extending furtheralong line 328 towards valves V3 and V4. While the single pump andsingle balance chamber system is desirable from the standpoint of havinga cassette that is simple and relatively inexpensive, it may not bedesirable to lose fresh dialysate especially if bagged sterilizeddialysate is used. It should be appreciated, however, that if thedialysate is made online, the drawback is less of a concern.

Referring now to FIG. 21, system 300 e includes an additional dialysatepump 390, which is dedicated to removing spent or effluent fluid fromthe dialyzer or hemofilter. Dialysate pump 370 in turn is dedicated topumping fresh dialysate. Dialysate pump 390 in one embodiment is aperistaltic pump, however, pump 390 may be of any of the types describedabove for dialysate pump 370. Moreover, while the alternative pumpconfiguration of system 300 e is shown for simplicity in combinationwith a single dialyzer 20 or 30, the pumping configuration of system 300e is compatible with any of the modalities set forth in FIGS. 17 to 20.

In the alternative pump arrangement of system 300 e, pump 390 pumpsspent fluid through line 328, valve V4 and into the spent compartment342 of single balance chamber 340. That action causes membrane 346 tomove and push an equal amount of fresh dialysate from fresh chamber 344through valve V1, line 314 and into the dialyzer or patient. At the endof the pump to patient cycle, all valves shut off. Afterwards, valves V2and V3 open allowing fresh dialysate pump 370 to pull fresh, heateddialysate from one of the supplies, through line 330, through valve V3and into fresh compartment 344. That action moves membrane 346 to pushspent dialysate from spent compartment 342 through valve V2 and line338, to one of the drain bags.

Each of the alternative configurations for the placement of pressurerelief 332 is equally applicable to the dual dialysate pump system 300e. In a further alternative embodiment (see FIG. 23), pressure relief332 is located instead from the outlet of dialysate pump 370 across tothe inlet side of heater 58. Here, pressure relief 332 connects to line330 between supply bags 14 to 18 and heater 58 and line 330 downstreamof pump 370.

To remove ultrafiltrate from the patient via the dual dialysate pumpsystem 300 e, with the spent compartment 342 full of effluent dialysate,valves V2, V3 and V5 are opened. Spent fluid pump 390 pumps effluentfluid through line 328, valve V5, line 348 and valve V3 into freshcompartment 344. Such action causes membrane 346 to move and pusheffluent fluid from compartment 342 through valve V2, line 338 and intoone of the drain bags. Because the source of matching fluid for thebalance chamber is used dialysate, that amount of matching fluid isremoved from the patient as ultrafiltrate.

It should be appreciated that after the ultrafiltrate stroke, the nextaction is to again pump spent fluid from the dialyzer or hemofilterthrough valve V4 into spent chamber 342. That action causes membrane 346to move and in turn pump one balance chamber volume worth of spent fluidfrom fresh compartment 344 (used previously to push the volume ofultrafiltrate) through line 314 to either the dialyzer or the patient.The spent dialysate still provides a clearance benefit to the patient,especially with respect to larger molecules, such as β₂M. This actionalso extends the life of a certain amount of the dialysate, which isbeneficial especially in the case of a home treatment using sterilizedand bagged fluid.

Referring now to FIG. 22, an alternative hybrid system 300 f isillustrated. System 300 f provides the single balance chamber 340 incombination with a dialysate fill pump 22, 24 and an ultrafiltrateremoval pump 26, 28. In an embodiment, the fill and removal pumps aremembrane pumps as described above. The volumetric pumps eliminate theneed for the additional valve V5 and ultrafiltrate line 348 in FIG. 21.Otherwise, the two systems are very similar, including the dedicateddialysate removal line 328 operating with pump 26, 28 and a dedicateddialysate fill line 330 operating with a dedicated pump 22, 24.

As with the other systems, system 300 f is operable with any of themodalities discussed herein and is illustrated only for convenience incombination with a single dialyzer 20, 30. The advantage of system 300 fis that there is no mixing of fresh and spent dialysate at the balancingchamber. It should be appreciated that even in FIG. 21, with a separatedialysate pump 390, a small amount of fresh solution will be mixed withspent dialysate during the ultrafiltrate cycle in which pump 390 pushesfluid through line 328, valve V5, line 348 and a small portion of line330 and valve V3 into fresh compartment 344. In FIG. 22, ultrafiltrationis performed by opening valve V6 and pulling a predetermined amount ofspent dialysate through pump 26, 28. Valves V3 and V4 are opened and allother valves are closed. Here, pump 26, 28 pushes spent dialysatethrough line 328 and valve V4 into the spent compartment 342 of singlebalance chamber 340. That action moves membrane 346, which pushes freshdialysate from fresh compartment 344 back through valve V3 and line 330.Afterwards, all valves are closed for an instant. Then valves V2 and V3are opened, enabling pump 22, 24 to push fresh dialysate into freshcompartment 344, forcing spent dialysate from compartment 342 to movethrough drain line 338 into one of the drain bags.

It is necessary in renal replacement therapies, such as hemodialysis toprovide a bolus of fresh solution to the patient for various reasons.For instance, the patient may need a bolus or volume of fluid if thepatient becomes hypovolemic (abnormally low volume of circulating blood)or hypotensive (low blood pressure). To provide a bolus of solution forsystem 300 f, fresh dialysate pump 22, 24 expels a predetermined amountof fluid, while valves V3 and V4 are opened and all other valves areclosed. The fresh dialysate travels through line 330, valve V3 and intofresh compartment 344 of balance chamber 340. That action causesmembrane 346 to move and push fluid back through line 328 and valve 324into effluent dialysate pump 26, 28. Afterwards, all valves are closed.Then, valves V1 and V4 are opened and effluent dialysate pump 26, 28pushes used dialysate into spent chamber 342 of balancing chamber 340.That action causes membrane 346 to move, pushing fresh solution fromfresh chamber 344 into the dialyzer. Since no ultrafiltration is removedin this cycle, the amount of fluid sent to the dialyzer represents a netgain or bolus of fluid for the patient. This process can be repeated asmany times as necessary to provide a patient with an overall net gain influid, if needed.

Previous FIG. 21 also illustrates one embodiment for providing a bolusof fluid to the patient. Here, an additional line 352 and valve V6 areprovided. To provide the bolus, valves V3 and V6 are opened, whilevalves V1, V2, V4 and V5 are closed. Fresh dialysate pump 370 causesfresh dialysate to fill through valve V3 into fresh chamber 344 ofbalance chamber 340. An equivalent amount of spent fluid is pushed viathat action and membrane 346 out of balance chamber 340, through line352 and valve V6 into line 314 and dialyzer 20, 30. Again, since noultrafiltration is removed in this cycle, the fluid sent to dialyzer 20,30 represents a net gain or bolus of fluid. It should be appreciatedthat spent or effluent dialysate, which is still sterile, is suitablefor the purpose of providing a bolus of fluid to the patient.

In an alternative embodiment, system 300 e of FIG. 21 can provide abolus of solution by opening valves V1, V4 and V5. Valve V3 is closed.Fresh dialysate pump 370 pumps fresh dialysate into spent compartment342. Then all valves are closed for an instant. Afterwards, valves V3and V6 are opened and fresh dialysate pump 370 pumps dialysate intofresh compartment 344, forcing the fresh fluid in spent compartment 342to flow through bolus line 352, valve V6 and line 314 into the dialyzer.System 300 e is also restored to balancing mode.

A number of alternative embodiments may be used with systems 300 a to300 f. Any of the dialyzers discussed herein, such as the single filterdisclosed in U.S. Pat. No. 5,730,712, assigned to the assignee of thepresent invention, may be used. Furthermore, the single dialyzerdiscussed below in connection with FIG. 32 may also be used. Arterialline 44 a in an embodiment includes an air sensor and clamp 54 forautomatic blood rinseback. Additionally, any of the fluid preparationand recirculation embodiments discussed above may be implemented withthe single balance chamber systems 300. Moreover, any of the alternativeembodiments listed above for systems 10, 110, 210, etc., may beapplicable to systems 300.

Systems 300 a to 300 f also include electrodes or contacts 354 and 356,which are used with an access disconnection sensor (“ADS”). ADS contacts354 and 356 are incorporated respectively in arterial line 44 a andvenous line 44 b. If one of the arterial or venous lines becomesdisconnected from the patient, an electrical impedance is changed. Thebreak of the loop is sensed, blood pump 48 is shut down andcorresponding clamps are closed. An alternative mechanism for thedetection of accidental needle disconnection is the use of a conductiveblanket underneath the patient's access. Any spillage of blood changesthe conductivity of the blanket, setting off an alarm and stopping thepumping of blood and dialysate.

Ultrafiltrate Control Single Balance Tube

The principles described above in FIGS. 17 to 22, covering systems 300,are applicable to different types of balancing apparatuses contemplatedby the present invention. Each of systems 300 employs a single balancechamber 340. Referring to FIG. 23, an alternative system 400 employs analternative balancing device 360. One embodiment for a balancing tube360 is shown and discussed in more detail below in connection with FIG.45. In general, balance tube 360 includes a cylindrical or otherwisetubular member. Inside such member resides a piston, ball or otherseparator 366 that fits snugly within the tube or cylinder. Balance tube360 includes a tube or cylinder having a fresh portion 362 and a spentportion 364. Separator 366 fits snugly within the tube and moves backand forth between the fresh side 362 and spent side 364 of the tube.

System 400 of FIG. 23 is configured in a similar manner to system 300 eof FIG. 21. Each component marked with an identical element numberperforms the same function and includes each of the same alternativesdescribed above in system 300 e. The primary difference between system400 and system 300 e as noted is the use of the balance tube 360 asopposed to balance chamber 340.

Valves V1 and V4 are opened, while valves V2, V3, V5 and V6 are closedfor the pump to dialyzer or patient cycle in system 400. Spent dialysatepump 390 pumps effluent dialysate through line 328 and valve V4 into thespent side 364 of balance tube 360. That action causes separator 366 tomove towards the fresh side 362 of balance tube 360 and push a likeamount of fluid out through line 314 and valve V1 into dialyzer 20, 30or directly to the patient (as before, system 400 of FIG. 23 isapplicable to any of the modalities discussed herein).

In the pump to drain cycle, valves V2 and V3 are opened, while valvesV1, V4, V5 and V6 are closed. Fresh dialysate pump 370 pumps fresh fluidthrough line 330 and valve V3 into the fresh side 362 of balance tube360. That action causes separator 366 to move towards the spent side 364of balance tube 360. A like amount of fluid is forced out of spent side364, through drain line 338 and valve V2 to one of the drain bags.

For the ultrafiltration cycle of system 400, valves V2, V3 and V5 areopened, while valves V1, V4 and V6 are closed. Prior to this cycle,effluent dialysate resides within balance tube 360 and separator 366 ispushed all the way to the fresh side 362 of the balance tube 360. Next,spent dialysate pump 390 pulls effluent dialysate from the dialyzer orhemofilter through line 328, through ultrafiltrate line 348 and valveV5, through fill line 330 and valve V3 into the fresh side 362 ofbalance tube 360. That action causes separator 366 to move towards spentside 364, pushing an equal volume of fluid out through valve V2 anddrain line 338 to one of the drain bags. Because the fluid sent to drainis matched with effluent dialysate from the dialyzer or ultrafilter, thefluid sent to drain constitutes fluid removed or ultrafiltered from thepatient.

For a bolus of fluid to the patient, valves V3 and V6 are opened, whilevalves V1, V2, V4 and V5 are closed. In essence, no fluid can be drawnfrom the dialyzer or hemofilter. Instead, fresh dialysate pump 370 pumpsfresh dialysate through line 330, through valve V3 and into the freshdialysate side 362 of balance tube 360. Such action causes separator 366to move towards side 364 of balance tube 360. A like volume of fluid ispushed from balance tube 360, through bolus line 352 and valve V6,through fill line 314 into dialyzer 20, 30 or directly into the venousline 44 b. Because the fluid delivered to the dialyzer or patient is notmatched with an amount of fluid removed from the dialyzer or hemofilter,the fluid delivered to the dialyzer or patient constitutes a net fluidgain or bolus for the patient. Such procedure is repeated as necessaryuntil the patient receives a needed amount of fluid. Any of thealternative bolus embodiments described above in connection with FIG. 21may also be used with system 400 and balance tube 360. Other features ofbalance tube 360 also applicable to system 400, such as end strokesensors, are shown below in connection with FIG. 28.

Ultrafiltrate Control Single Tortuous Path

Referring now to FIG. 24, a further alternative flow balancing device isillustrated by system 450. System 450 employs a single tortuous path470. System 450 includes many of the same components described above,such as drain bag 12, supply bags 14 to 18, fresh dialysate pump 370,heater 58, spent dialysate pump 390 and blood pump 48. System 450 isshown in use with the ECHD dual dialyzers 20 and 30, separated by avariable restriction 40. It should be appreciated that system 450 may beoperated with any of the modalities described herein. Other componentswith like element numbers are also shown.

The primary difference between system 450 and the previous singlebalance device systems is the use of a tortuous path 470 as opposed to aconfined volume that is divided by a separator, such as a membrane ormoving ball or piston. The advantage of system 450 is that to placetortuous path 470 in a cassette is relatively simple compared witheither the volumetric membrane pumps or the balance chambers and tubesdescribed above, which each require a flexible sheeting or membrane tobe sonically welded, chemically adhered or otherwise fused to a rigidplastic cassette.

Tortuous path 470 as seen in FIG. 24 includes a combination ofultrafiltrate line 328 and dialysate input line 330. Fluid line 328,330is sized to provide as best a bulk transport of fluid as possible, whileattempting to minimize pressure drop. That is, a tortuous path 470 in anembodiment is a U-shaped, V-shaped or rectangular-shaped channel in thecassette, which is relatively long and thin or of a small diameter orcross section. The goal of tortuous path 470 is to allow one bulkinfusion of fluid, such as fresh dialysate, to move a bulk of fluidalready existing in the flow path to a desired place, such as spentdialysate to drain.

A drawback of tortuous path 470 of system 450 is the potential for freshdialysate and spent dialysate to mix within the tortuous path as opposedto moving as bulk fluids. The configuration of the path is refined sothat such mixing is minimized and occurs as much as possible only at theinterface between the fresh and used dialysate, leaving the middle ofthe bulk of either fluid relatively unmixed and consistent. To this end,measures may be taken to maintain the flow of both fluids in either alaminar or turbulent state as desired to minimize mixing. For the onlinesystems described herein especially, tortuous path 470 offers a viablesolution, wherein the cost and complexity of a cassette or volumetriccontrol system is reduced.

To perform the fill to dialyzer or patient cycle in system 450, freshdialysate is pumped via dialysate pump 370 through line 330 and valve V2up to closed valves V7 and V9. Next, valves V5 and V9 are opened, whilevalves V2 and V7 are closed. Spent dialysate pump 390 pulls effluentdialysate from arterial dialyzer 30 through line 328, valve V5, tortuouspath line 328, 330 and up to valve V9. That bulk transport of fluidpushes the fresh dialysate residing within tortuous path line 328, 330through valve V9, through fill line 314 and into venous dialyzer 20 orvenous line 44 b.

After the fill cycle takes place, tortuous path line 328, 330 is filledwith effluent or spent dialysate. The drain cycle may then take place.Here, valves V5 and V9 are closed, while valves V2 and V7 are opened.Fresh dialysate pump 370 pumps fresh, heated dialysate through valve V2,line 330, through tortuous path line 328, 330 and up to the point ofvalve V9 or V7. That bulk transport of fluid in turn pushes spentdialysate through drain line 338 and valve V7 into one of the drainbags.

The ultrafiltrate cycle takes place as follows. With the tortuous pathline 328, 330 filled with ultrafiltrate, valves V5 and V7 are opened,while valves V2 and V9 are closed. Spent dialysate pump 390 pulls fluidfrom arterial dialyzer 30 through line 328, valve V5 to fill tortuouspath line 328, 330. That amount of fluid is then moved through valve V7,line 338, to drain. Because the amount of fluid moved to drain ismatched at least substantially by effluent or spent dialysate, thepatient experiences a net loss or ultrafiltration of fluid.

To provide a bolus of fluid to the patient, with the tortuous path line328, 330 full of fresh or effluent fluid, valves V5 and V7 are closed,while valves V2 and V9 are opened. Fresh dialysate pump 370 pumps freshdialysate through line 330 and fills tortuous path line 328, 330. A samevolume or substantially the same volume of fluid flows through valve V9,fill line 314 and into venous dialyzer 20. Because the patient ordialyzer has received an amount of fluid without a corresponding amountof fluid being withdrawn from arterial dialyzer 30, patient 42experiences a net gain or bolus of fluid.

Ultrafiltrate Control Dual Balance Chambers

One potential problem with the single balancing device embodiments justpreviously described is pulsatile flow. The single balancing devicesystems can compensate the pulsatile nature of the flow somewhat byslowing the flowrate of fresh fluid to the dialyzer relative to theflowrate of fluid from the dialyzer. Other solutions are provided bysystem 500 of FIG. 25 and other dual balance device systems shown below.These systems provide two balance chambers, two balance tubes or twotortuous paths that operate in parallel and at alternating cycles sothat flow is delivered to the dialyzer or patient as it is being removedfrom the dialyzer or hemofilter. System 500 includes many of the samecomponents described above, which are shown with like numbers that donot need to be re-described. Further, system 500 is shown in operationwith the ECHD dual high flux dialyzers 20 and 30 and variablerestriction 40. It should be abundantly apparent however from theprevious descriptions that system 500 can operate with any of themodalities described herein.

System 500 includes first and second balance chambers 340 a and 340 b,which are each the same in one embodiment as balance chamber 340described above in connection with FIGS. 17 to 22. Balance chambers 340a and 340 b may be referred to herein collectively as a flow equalizer.

In the illustrated embodiment, dialysate pumps 370 and 390 areperistaltic pumps. They may alternatively be membrane pumps or othertypes of pumps described herein. Fresh dialysate pump 370 is shownupstream of heater 58, which is different from the single balance deviceconfigurations. Either configuration is possible for either of thesingle and double balance device systems. Further, each of the valvesused in system 500 may be configured in a cassette or be any type ofvalve as discussed herein.

In a first exchange cycle, one of the balance chambers 340 a or 340 bfills with fresh solution and at the same time delivers an equal volumeof spent dialysate to drain. In that same first cycle, the other balancechamber 340 a or 340 b fills with effluent dialysate and at the sametime pushes a like volume of fresh dialysate to the dialyzer 20 or thepatient according to the modality. Then, in a second cycle, the balancechambers 340 a and 340 b alternate functions so that the balance chamberthat previously delivered fresh dialysate to the patient now deliversspent dialysate to drain, while the balance chamber that previouslydelivered spent dialysate to drain now delivers fresh dialysate to thedialyzer or patient.

Based on the foregoing description of the operation of balance chamber340 in connection with FIGS. 17 to 22, it is not necessary to repeat thevalve description for each of the balance chambers 340 a and 340 b ofsystem 500. One important aspect to distinguish, however, is that thereis a short dwell time at the end of each exchange cycle when all valvesare closed to ensure that the two balance chambers 340 a and 340 b arein sync for the next cycle.

The flow equalizer or balance chambers 340 a and 340 b are useddifferently than in other systems employing a flow equalizer from thestandpoint that there is not a separate UF removal device in system 500.That is, in other systems employing a flow equalizer or dual balancechambers, the balance chambers are dedicated to removing an amount offluid from the dialyzer, while at the same time filling the dialyzerwith a like amount of fluid. System 500, on the other hand, uses balancechambers 340 a and 340 b for that purpose and also to remove a netamount of fluid or ultrafiltrate from patient 42. The valve operationfor removing a net loss or ultrafiltration of fluid from the patientincludes opening valves V1, V2, V6, V7, and V9, while closing valves V3,V4, V5, V8 and V10. This valve configuration pushes effluent dialysateto drain by pushing the fresh dialysate from balance chamber 340 b tobalance chamber 340 a.

The systems herein including system 500 having dual balancing chambers340 a and 340 b enable an ultrafiltrate removal rate to vary over time,which is sometimes referred to as an ultrafiltrate profile. For example,if an ultrafiltrate cycle is typically performed after each fiveexchange cycles, one could change the rate at which ultrafiltrate isremoved from the patient by increasing or decreasing the frequency ofcycles. This could result, for example, in more fluid being removedduring a first part of therapy than a second. In the present invention,the processor of the renal failure therapy machine may be configured torun an algorithm, which enables the patient to select a profile, atreatment time and an overall volume to be removed. The algorithmautomatically calculates an ultrafiltrate frequency profile thatachieves, according to the profile, an entered net cumulativeultrafiltrate volume over an entered treatment time. Those parametersmay be entered through a patient data card or through a secure dataconnection.

System 500 can also provide a bolus of solution to the patient whenneeded. Valves V2, V3, V7, V8 and V10 are opened and valves V1, V4, V5,V6 and V9 are closed. Pump 370 is run forcing one balance chamber bolusof dialysate and/or substitution fluid to the dialyzer or patient.

In any of the embodiments described herein, it is important that thevalves of the systems are checked to ensure that they open and closeproperly. In one embodiment, the valves are checked periodicallythroughout treatment using conductive sensing. That is, if fluid escapesfrom the system via a faulty valve or tear in a cassette membrane,conductive sensors that measure a flow of electricity across a liquidcan send an alarm and trigger appropriate action. Further, with acassette, temperature sensing may be employed, for example, by applyinga thermistor, IR sensor or thermocouple on one side of the sheeting ofthe cassette. Here, the temperature sensor is attached to the bloodtherapy instrument and, for example, contacts the sheeting membrane soas to obtain a quick reading of the temperature of the dialysate.

Prime and Rinseback

Referring now to FIG. 26, it is necessary to prime the extracorporealcircuits of the present invention with sterile solution prior toconnecting patient access line 44 a and venous access line 44 b to thepatient. To do so, the ends of the arterial and venous lines areconnected together at connection 358. In one embodiment, fresh dialysatepump 370 and effluent dialysate pump 390 run and pump fluid throughbalance chambers 340 a and 340 b (or through any of the single or dualbalance devices discussed herein) until dialysate or substitution fillsthe dialysate circuit. The blood therapy machine then enters a bolusmode. In one embodiment, blood pump 48 runs in reverse until venous dripchamber 52 fills with fluid. Excess air in the line and drip chambervents through a transducer protector or vent 64 provided with or incommunication with drip chamber 52. Transducer protector or vent 64 inone embodiment is a 0.2 micron hydrophobic membrane.

In the next step of this first priming method of the present invention,blood pump 48 runs in its operational direction until half the volume ofthe drip chamber is moved. Then, blood pump 48 runs in the reversedirection again until drip chamber 52 is again filled and vented. Thepump then runs again in the normal operation direction enough to movehalf a drip chamber volume worth of fluid in the normal operatingdirection. In each cycle, dialysate or substitution fluid isback-filtered through dialyzer 20, 30 (or different filter for adifferent modality), adding to the total volume of fluid in theextracorporeal circuit over each cycle period. This first priming methodcycles back and forth as described until the extracorporeal circuit iscompletely filled with dialysate or substitution fluid. It should beappreciated that this priming method applies to any of the modalitiesdescribed herein, any of the pumping arrangements described herein andany of the volumetric control methods described herein.

In a second priming method, a separate saline or priming fluid bag 368is connected to the extracorporeal circuit via saline line 372. In theillustrated embodiment, saline line 372 tees into the extracorporealcircuit at two places, upstream and downstream of blood pump 48. ValvesV11 and V12 are positioned in saline line 372 so as to allow saline toflow selectively to one of or both of the teed connections upstream anddownstream of blood pump 48. Arterial access line 44 a is againconnected to venous access line 44 b via connection 358.

In the operation of the second priming method of the present invention,valve V11 located downstream of pump 48 is opened, enabling blood pump48 to run in reverse and pump saline from bag 368, through saline line372, through valve V11 through access line 44 a, through connection 358,through access line 44 b, and into drip chamber 52. Blood pump 48 pumpssaline until drip chamber 52 is full and air is purged via vent 64.Next, valve V11 and air detector clamp 53 are closed and valve V12 isopened, enabling blood pump 48 to pull saline from bag 368 and push thatvolume of fluid in the normal operating direction downstream of pump 48,venting air through vent 64. This cycle continues until theextracorporeal circuit is fully primed. It should be appreciated thatthis second priming method is equally applicable to any of themodalities, pumping regimes, and volumetric control methods discussedherein.

Modifications to either of the first and second priming methods can alsobe made to provide a blood rinseback to patient 42 this is done at theend of therapy to return any blood in the extracorporeal line to thepatient. The primary difference for blood rinseback is that access lines44 a and 44 b are connected to patient 42 instead of to each other viaconnection 358. For example, using saline 368 or other suitable source,valve V11 is opened and pump 48 runs in reverse to rinseback blood tothe pre-pump portion of arterial line 44 a. An air detector 54 in thatportion of arterial line 44 a detects any air in the blood or saline andclamps the circuits if such air is detected. Pump 48 runs for anappropriate amount of time to ensure that blood has been fully rinsedback to the patient through the pre-pump portion of arterial line 44 a.

Next, valve V11 closes and valve V12 opens, enabling pump 48 to pullsaline from supply 368 and operate in the normal direction. Pump 48pumps saline or other suitable fluid from source 368 through theremaining portion of arterial line 44 a, through dialyzer 20, 30(depending on modality) and through venous line 44 b including dripchamber 52. The rinseback returns blood from those portions of theextracorporeal circuit to patient 42. In an embodiment, saline sensorson the arterial and venous lines 44 a and 44 b, respectably, cause analarm if the extracorporeal circuit is not clear or transparent after apreset amount of rinseback. After blood is fully rinsed back to thepatient, the patient is instructed to disconnect from the renal failuretherapy system of the present invention.

The first priming method described above may also be adapted for bloodrinseback. Here either dialysate or saline is back-filtered through thedialyzer or other modality filter. Blood pump 48 is run in the reverseand forward cycles described above in connection with the first primingmethod. Pump 48 may be run at a slower speed for blood rinseback so asto limit an amount of mixing between saline and blood. The saline orother solution needed to fully rinseback the blood to the patient isthereby minimized.

In an alternative method for priming system 500 or rinsing back blood tothe patient, one of the line clamps 54 in the extracorporeal circuit isclosed and saline or dialysate is pumped via one or both dialysate pumps370 and 390 into the extracorporeal circuit until drip chamber 52 fillsto a preset level, such as ¾ full. After the drip chamber 52 is filledto the preset level, the dialysate or saline infusion is stopped, andpumps 370 and 390 no longer pump fluid into the extracorporeal circuit.Then, line clamp 54 is opened. Blood pump 48 circulates the dialysatethrough the extracorporeal circuit. If needed, line clamp 54 may beclamped again to repeat the process.

In a further alternative prime or rinseback embodiment, saline bag 368,dialysate from a supply or drain bag, saline line 372, valve V12 and theportion of line 372 leading to the extracorporeal circuit between clamp54 and blood pump 48 are used. Here, valve V11 in FIG. 26 is not needed.Dialysate or saline is pumped via one or more of the dialysate pumps 370and 390 through dialyzer 20,30 with blood pump 48 running in the reversedirection and valve V12 closed so as to prime or rinseback the arterialline 44 a. Then, valve V12 is opened and saline or dialysate is pulledfrom supply bag 368 with pump 48 running in the normal operatingdirection to prime or rinseback venous line 44 b. This method usesdialysate or saline pumped through the dialysate circuit as well as adialysate or saline source running directly to the extracorporealcircuit. This embodiment eliminates valve V11 shown in system 500.

It should be appreciated that each of the forgoing methods of prime andrinseback may be used in any of the forgoing modalities, pumpconfigurations and volumetric control schemes. Further, those of skillin the art may be able to determine additional valving operations toachieve an effective prime and rinseback using the apparatuses andmethods of the present invention.

Ultrafiltrate Control Dual Balance Tube

While the present invention sets forth multiple embodiments forbalancing devices, it is believed that the balancing tubes provide agood trade-off between ease of manufacturing, cost and effectiveness.The balancing chambers shown previously for example in FIGS. 25 and 26are time-tested and proven to effectively meter and controlultrafiltrate in blood kidney failure therapies, such as hemodialysis.The sheeting and chambers associated with balance chambers, whilecertainly manufacturable, present a more complicated cassette thansimply one having valve chambers, tubing for peristaltic pumps and tubesfor the balance tubes of the present invention.

The tortuous path embodiment, while perhaps involving the simplestcassette, may not be as desirable with respect to efficient use of freshdialysate (due to the tendency of the fresh and effluent dialysates tomix). Again, this potential drawback is not as much of a concern whendialysate is made online. The balance tubes may offer the best solutionhowever for home use with fresh dialysate bags.

Referring to FIGS. 27A to 27D, different flow cycles pertinent tovolumetric control of dialysate using dual balance tubes areillustrated. It should be appreciated that the layout of valves V1 toV10 with respect to balance tubes 360 a and 360 b is the same as thelayout of valves V1 to V10 with respect dual balance chambers 340 a and340 b in FIGS. 25 and 26. One can therefore readily visualize balancetube 360 a being used in place of balance chamber 340 a and balance tube360 b being used in place of balance chamber 340 b in FIG. 25.

The cycle shown in FIG. 27A is a first dialysate exchange cycle. Here,valves V1, V4, V5, V8, V9, and V10 are open while valves V2, V3, V6 andV7 are closed. At the start of this cycle balance tube 360 a is filledwith fresh dialysate and separator 366 a is located at leastsubstantially at the end of spent portion 364 a. Also, balance tube 360b is filled with effluent dialysate and separator 366 b is located atleast substantially at the end of fresh portion 362 b of balance tube360 b. In this first cycle, fresh dialysate pump 370 pumps freshdialysate through line 330, line 330 b and valve V5 into fresh dialysateportion 362 b of balance tube 360 b. The force of fluid entering freshportion 362 b pushes separator 366 b, which in turn pushes spentdialysate through open valve V8, line 338 b, manifold 338 and valve V9to one of the drain bags.

At the same time spent dialysate pump 330 pushes effluent dialysate froma dialyzer or hemofilter through manifold 328, line 328 a, valve V4 andinto the spent portion 364 a of balance tube 360 a. The force of fluidentering spent portion 364 a of balance tube 360 a causes separator 366a to move towards the fresh portion 362 of balance tube 360 a. In turn,fresh dialysate is pushed through valve V1, line 314 a, manifold 314 andvalve V10 to a dialyzer or the extracorporeal circuit, depending on themodality used. It should be appreciated from the valving description ofFIG. 27A that one of the balancing chambers is metering fresh fluid tothe patient, while the other balancing chamber is metering spent fluidto drain.

FIG. 27B shows separators 366 a and 366 b at the fresh end 362 a andspent end 364 b of balance tubes 360 a and 360 b, respectably (at theend of travel of the cycle shown in FIG. 27A). At this moment all valvesV1 to V10 are closed. The all valves closed sequence ensures thatbalance tubes 360 a and 360 b and valves V1 to V10 are in sync for thenext fluid transport cycle.

Referring now to FIG. 27C, an opposite fluid transport cycle of thatshown in FIG. 27A is illustrated here beginning from the valveconditions shown in FIG. 27B, namely, with balance tube 360 a filledwith effluent dialysate and balance tube 360 b filled with freshdialysate. The opposite flow now occurs in which balance tube 360 ameters spent fluid to drain, while balance tube 360 b meters fresh fluidto the dialyzer or extracorporeal circuit. In this cycle, valves V2, V3,V6, V7, V9, and V10 are open, while valves V1, V4, V5 and V8 are closed.Fresh dialysate pump 370 pumps fresh dialysate through manifold 330,line 330 a and valve V3 into the fresh portion 362 a of balance tube 360a. Such action causes separator 366 a to push spent dialysate throughvalve V2, line 338 a, manifold 338 and valve V9 to drain. At the sametime, spent dialysate pump 390 pumps spent dialysate from a dialyzer orhemofilter through manifold 328, line 328 b, valve V6 and into the spentor effluent portion 364 b of balance tube 360 b. Such action causesseparator 366 b to push fresh dialysate through valve V7, line 314 b,manifold 314 and valve V10 to the patient or dialyzer.

After the cycle of FIG. 27C is completed each of the valves closes withthe balance tubes in the same state shown in FIG. 27A, so that the abovethree cycles shown in FIGS. 27A and 27C can be repeated. It should beappreciated that the all valves closed state of FIG. 27B occurs for arelatively short period of time, so that the flow of fluid to thepatient or dialyzer and from the dialyzer or hemofilter is substantiallynonpulsitile. Such nonpulsitile flow is advantageous versus therelatively pulsitile flow of the single balance device systems because(i) treatment is administered more efficiently and (ii) the fresh andspent pumping cycles may be carried out at the same speed reducing therisk of pulling too much fluid from the patient.

Referring now to FIG. 27D, one embodiment for performing ultrafiltrationwith the dual balance tubes 360 a and 360 b of the present invention isillustrated. It should be appreciated that the state of separators 366 aand 366 b and the fluids held within balance tubes 360 a and 360 b isthe same as in FIG. 27A. Instead of performing the exchange cycle,however, the valve arrangement shown in FIG. 27D is employed. Here,valves V1, V4, and V7 to V9 are opened, while valves V2, V3, V5, V6 andV10 are closed. In the ultrafiltration cycle only used dialysate pump390 is run. Pump 370 may stop or run through recirculation line 332.Pump 390 pumps effluent fluid through manifold 328, line 328 a and valveV4 to push separator 366 a from spent portion 364 a of balance tube 360a towards fresh portion 362 a of the tube. That action causes freshdialysate through valve V1, line 314 a, manifold 314, line 314 b andvalve V7 into balance tube 360 b. Fluid entering balance tube 360 inturn pushes separator 366 b, forcing effluent fluid through valve V8,line 338 b and manifold 338 to drain through valve V9. The fluid sent todrain represents ultrafiltrate because during that cycle nocorresponding amount of fluid is sent to the patient or dialyzer.

This ultrafiltrate cycle may be varied in frequency relative to thefluid exchange cycles to vary the rate of ultrafiltrate removal overtime. It should be appreciated that a bolus of fluid may be given to thepatient in a similar manner, with incoming fresh dialysate pushingeffluent dialysate via a separator from one balance tube to the other,forcing the separator in the other balance tube to push fresh solutiontowards the dialyzer or extracorporeal circuit depending on modality.The patient or dialyzer gains fluid without a corresponding loss offluid from the patient, resulting in a bolus of fluid.

Referring now to FIG. 28, an alternative valve configuration for balancetube 360 a of the present invention is illustrated. Here, a pair of tees374 are mated or sealed to the ends 362 a and 364 a of balance tube 360a. Valves V1 to V4 are placed in the same configuration relative to theinlets and outlets of tube 360 a shown in FIGS. 27A to 27D. Here, onlyone pathway to each end 362 a and 364 a of balance tube 360 a is needed.As in FIGS. 27A to 27D, valve V2 controls whether effluent dialysate isdelivered to the drain or the drain bag through line 338. Valve V4controls whether effluent dialysate from the dialyzer or hemofilterenters balance tube 360 a through line 328 a. Valves V2 and V4 are bothlocated at the spent dialysate end 364 a of balance 360 a. Valve V3controls whether fresh dialysate from one of the supply bags entersbalance tube 360 a through line 330 a. Valve V1 controls whetherdialysate leaves balance tube 360 a through line 314 a. Valves V1 and V3are both located at the fresh dialysate end 362 a of balance 360 a.

FIG. 28 also illustrates that a pair of sensors 376, such as opticalsensors, are positioned in the instrument so as to detect and ensurethat separator 366 a has traveled to the appropriate end 362 a or 364 aof balance tube 360 a. For example if fluid is expected to be receivedfrom the dialyzer through line 328 a and V4, the logic in the renalfailure therapy machine will expect to see a beam of light of the sensor376 at end 362 a broken and then reestablished once separator 366 apasses sensor 376 and reaches the end of its stroke. If the beam oflight is either not broken or not reestablished the machine knows thatseparator 366 a has not traveled to its appropriate destination for thegiven cycle and sends an appropriate signal. Alternative sensors, suchas proximity, capacitance, Hall Effect, ultrasound or others may beemployed instead of the illustrated optical sensors 376. These sensorsmay also be employed to check valve function. Here, if separator 366 amoves due to a valve being open when that valve is supposed to beclosed, the valve is detected to have a leak.

Ultrafiltrate Control Dual Tortuous Path

Referring now to FIG. 29, another dual balance device embodiment isillustrated. Here the balance chambers and balance tubes shownpreviously in FIGS. 25 to 28 are replaced by a pair of tortuous paths470 a and 470 b. Tortuous paths 470 a and 470 b are placed in betweenvalves V1 to V8 as seen also in FIGS. 25 and 26. Indeed, the operationof valves V1 to V8 in FIGS. 25, 26 and 29 operate identically tocontinuously send fluid to the patient, send spent fluid to drain andremove ultrafiltrate from the dialyzer or hemofilter. As before, thedual tortuous paths 470 a and 470 b may be implemented with any modalityand with any of the different types of pumps described herein. To pushfresh fluid to dialyzer 20, 30, torturous tortuous path line 328 a, 330a or line 328 b, 330 b is filled with fresh dialysate. Either valves V1and V4 for tortuous path 470 a or valves V6 and V7 for tortuous path 470b are opened. Pump 390 pumps spent dialysate through either line 328 a,330 a or line 328 b, 330 b to push the corresponding bulk of freshdialysate to the dialyzer. Then either valves V2 and V3 or valves V5 andV8 are opened to push spent fluid to drain.

In one preferred embodiment, the tortuous paths 470 a and 470 b arealternated so that one path delivers dialysate to the dialyzer duringone cycle and the other tortuous path delivers dialysate to the dialyzerduring the same cycle. The roles of paths 470 a and 470 b are thenreversed. While one path is delivering dialysate to the dialyzer, theother is filling with fresh solution and delivering spent dialysate todrain. Each of the tortuous paths 470 a and 470 b is built to have alength and diameter that attempts to minimize the amount of mixingbetween fresh and spent fluids, so that the fluids tend to move in bulkto their desired destination.

To remove ultrafiltrate, fresh fluid from one line 328 a, 330 a or 328b, 330 b can be moved to in turn displace spent fluid from the otherline to drain. For example, valves V1 and V4 of tortuous path 470 a maybe opened so that spent dialysate enters line 328 a, 330 a and displacesfresh dialysate through open valve V7 into line 328 b, 330 b of tortuouspath 470 b. Valve V6 is opened and spent dialysate is moved through line572 to drain. If needed, a valve may be added after dialysate pump 390so that spent fluid does not flow back into pump 390 during theultrafiltrate cycle.

As illustrated, a separate ultrafiltrate pump 570 may be added to system550 or to any of the forgoing systems. Ultrafiltrate pump 570 enablestortuous paths 470 a and 470 b to operate continuously to send fluid toand take equal amounts of fluid from the dialyzer or hemofilter. Theultrafiltrate pump 570 removes dialysate through ultrafiltrate line 572to one of the drain bags. It is believed that removing the ultrafiltratefunction from the tortuous paths 470 a and 470 b may reduce mixing ofthe fresh and spent fluids. The additional ultrafiltrate pump 570 canalso be run in reverse with pump 390 to provide a bolus of fluid to apatient in need same.

It should appreciated that any of the dual balancing device systemsdescribed herein can employ the ADS contacts 354 and 356 and associatedelectronics to detect when one of the access lines 44 a or 44 b isinadvertently disconnected from the patient during treatment. Further,any system can employ one of more of the various pressure reliefs 332shown in FIGS. 25, 26 and 29 and described previously. Furthermore, theheater may be placed before or after fresh dialysate pump 370. Again thepumps may be of any of the varieties described herein. Moreover, any ofthe dual balance device systems may be used with any of the fluidpreparation modules described above as well as the recirculation loops.The systems may also employ noninvasive temperature measuring devices tomeasure the temperature of fluid within a disposable cassette.

Ultrafiltrate Control Weight Scales

Referring now to FIGS. 30 and 31, a further alternative method ofcontrolling the amount of dialysate exchanged and ultrafiltrate removedis to do so by measuring the weight of fluid within supply and drainbags 12 to 18. For convenience only supply/drain bags 14, 16, and 18 areshown in FIG. 30. It is well known to use weight to control a renalfailure therapy process. A single scale can be employed that accountsfor both fresh fluid lost and spent fluid gained. Here, because a netvolume of fluid is removed or ultrafiltered from the patient, the systemexpects to see an increase in weight over time. Alternatively, a firstscale for the fresh bags and a second scale for the drain bags are used.Two signals are produced and summed to determine the amount ofultrafiltrate accumulated for any give point in time. The system ofFIGS. 30 and 31 uses a single scale, however, the dual scale approachmay be used instead.

The import of FIGS. 30 and 31 is to show one apparatus by which a scaleor weight measuring device may be implemented into the various systemsdescribed herein. In FIG. 30, a blood treatment machine 140 isillustrated. In the illustrated embodiment, blood machine 140 accepts acassette at cassette loading portion 142, which is on a front, angledpart of machine 140. Other embodiments of a machine that can accept adisposable cassette and employ a scale are shown below in FIGS. 35 to39. Bags 14, 16 and 18 are loaded onto stand 144. Stand 144 is coupledto a shaft 146.

FIG. 31 shows an enlarged view of the cutaway in FIG. 30 and that shaft146, stand 144 and the bags are supported by a foot 152 that rests on atable of wherever machine 140 is placed for treatment. Shaft 146 ismovable linearly within a linear bearing 148. A cap 154 having aplurality of anti-rotation pins 162 is fitted to the end of movableshaft 146. Pins 162 reside within mating slots or grooves defined in thehousing of machine 140. Pins 162 and the mating slots or grooves enableshaft 146 to move linearly but not rotationally with respect to machine140.

A seat 164 seals one end of a rolling diaphragm 168 between the seat andcap 154. A housing 176 coupled to foot 152 and the machine frame sealsthe other end of rolling diaphragm 168 between housing 176 and the frameof machine 140. Housing 176, rolling diaphragm 168 and seat 164 form aclosed volume chamber. The rolling diaphragm enables the volume toremain closed and also enables shaft 146 to fluctuate up and down due tothe varying weight within the supply end drain bags. The rollingdiaphragm 168 may be made of any suitable deformable but impermeablematerial, such as rubber or plastic sheeting. The volume of air withinthe closed volume chamber pressurizes due to the weight of the bags 14to 18 and supporting apparatus. The amount of pressure indicates orvaries with the amount of liquid in bags 14 to 18.

A pressure sensor, which may be any suitable type of sensor (notillustrated), is provided for example within opening 178 defined by seat164. The pressure sensor senses the amount of pressure within the closedvolume chamber. The sensor sends a signal to a processor or a controllerwithin machine 140, which processes that signal and determines thecorresponding weight in bags 14 to 18.

The weight control system is desirable because it removes the need forthe volumetric control devices described above. The cassette for machine140 is much simpler, including mainly valve flow paths. One disadvantageof the weight system is that it requires the patient to load the bagsproperly onto stand 144. The stand and assembly described in connectionwith FIGS. 30 and 31 may also add weight and size to the overall device.The home renal failure therapy machine of the present invention isdesirably small and light, so that a person can travel or maneuver thedevice easily within or outside of the home.

ECHD Filter

Referring now to FIG. 32, one embodiment for an ECHD filter isillustrated by filter 600. As incorporated above, one suitable ECHDfilter is described in U.S. Pat. No. 5,730,712, assigned to the assigneeof the present invention. Filter 600 like the filter described in thepatent is provided in a single unit. Filter 600 however differs from theone in the patent in that it allows for operation with a variablerestriction 40.

Filter 600 includes a housing 602 corresponding to venous dialyzer 20and a housing 602 corresponding to arterial dialyzer 30. Housing 602 maybe made of any suitable material, such as a cylindrical, rigid plastic.Fibrous, semi-permeable membranes are loaded within the venous section20 and the arterial section 30. Those membranes are potted at theoutside ends of housings 602 via a potting 604 according to any methodknown to those of skill in the art. The membranes are potted at theinside ends of each of the venous 20 and arterial 30 sections of filter600 via a potting 606.

A blood entry cap 608 is fixed in a sealed manner to housing 602 so thatblood may enter cap 608 via a blood tube, be dispersed within the capand enter the inside of the hollow semi-permeable fiber membranes ofarterial section 30. At the same time, blood is blocked from enteringhousing 602 on the outside of hollow fiber membranes via potting 604.

Blood travels through filter 600 via the arrow shown in FIG. 32. Thatis, blood travels upward through the arterial portion 30 of filter 600and out internal potting 606 of the arterial portion 30. Blood thenenters in-intermediate chamber 642. The intermediate chamber 642 is aband or outer tube that is secured sealingly to the internal ends ofhousings 602.

Blood then enters the second set of hollow semi-permeable membraneshoused within venous portion 20 of filter 600. The blood enters thosefibers and is prevented from entering housing 602 of venous portion 20outside the fibers via internal potting 606 at the internal end ofhousing 602 of venous portion 20. Blood flows through the venous portionof the membranes, through an outer potting 604 and into a blood exit cap632. Blood exit cap 632 in turn couples sealingly to a tube that carriesthe blood away from filter 600 within the extracorporeal circuit.

Housing 602 of venous portion 20 includes a dialysate entry port 634 anda dialysate exit port 636. Likewise, housing 602 of arterial portion 30includes a dialysate inlet port 638 and a dialysate exit andultrafiltrate port 640. Ports 634, 636, 638 and 640 may be of anysuitable type for mating sealingly with a medical fluid tubing. Port 634receives dialysate from the dialysate supply. Port 640 enables dialysateand ultrafiltrate from the patient to be pulled out of filter 600. Theeffluent dialysate stream exists filter 600 via port 640.

Variable restriction 40 is placed in fluid communication with ports 636and 638. The restriction may be made more or less restrictive so as tobackfilter greater or lesser amounts of fresh dialysate into the hollowfiber membranes located in housing 602 of venous portion 20. Asdescribed above, the clearance of filter 600 is convective anddiffusive. Filter 600 achieves one desired goal of the presentinvention, namely, to provide an overall effective treatment of small,middle and large molecules of a patient's waste via both convective anddiffusive clearance modes. Housings 602, caps 632, 608, the pottingmaterial, the porous fibers and the ports may be made of any suitablematerials.

Apparatus for Providing Variable Flow Restriction

Referring now to FIG. 33, one embodiment for variable flow restriction40 is illustrated. While it is contended that there are likely manydifferent ways to provide a repeatable and accurate variable flowrestriction, variable restriction 40 of FIG. 33 provides onesuitable-configuration. System 40 includes a stepper motor 954, which iscoupled to a lever arm 956 via a coupler 958. Stepper motors are knownin the art as highly accurate and repeatable positioning devices thatcan receive signals from a microprocessor that commands stepper motor954 to turn a precise distance, and perhaps at a desired accelerationand velocity. In FIG. 33, stepper motor 954 is used primarily toposition lever arm 956 to a precise position with respect to a fixedsurface 960.

A tube section 962 shown also in FIGS. 1, 4, 5, 9, 12 and 14, connectsdialysate flow between dialyzers 20 and 30. FIG. 33 illustrates thatsection 962 is held in place against surface 960 via bracket 964. Leverarm 956 as seen in FIG. 33 is currently in a position that enables fullflow through tube section 962. That is, in the configuration illustratedin FIG. 33, very little dialysate would backflow through the membranesof one of the dialyzers 20 or 30. As lever arm 956 is rotated in acounterclockwise direction as seen in FIG. 33, tube section 962 deformsand increasingly decreases in cross-sectional area, causing the amountof restriction in device 40 to continuously increase. Indeed, lever arm956 could be rotated to a point that would virtually restrict all flowthrough tube section 962, forcing virtually all of the therapy fluid toenter the extracorporeal circuit 50 through the membranes of one of thedialyzers 20 or 30.

Importantly, stepper motor 954 is accurate and repeatable. That is,stepper motor 954 can be commanded to rotate lever arm 956 to virtuallythe same position time and time again. Because tube section 962 is heldin the same position via bracket 964 relative to lever arm 956 and fixedsurface 960, lever arm 956 accurately and repeatedly creates the sameamount of restriction through line 962 when the arm 956 travels to thesame commanded position. The programmable nature of stepper motor 954also enables restriction 40 to have virtually any desired restrictionprofile that varies over the duration of therapy as desired by thepatient, physician or other operator. Such variable restriction profilesare described above and can be stored as programs within a memory deviceof the controller of the systems described herein, such that one of thevariable restriction profiles can be called upon and implemented asdesired.

Interfacing Between Cassette Blood Treatment Machine and Solution Bags

Referring now to FIG. 34, cassette 100 a (shown above in FIGS. 2 and 3)is shown in an operable position interfaced with a number of the flowdevices that are located inside of the blood treatment machine. Cassette100 a as illustrated includes a housing 104. Attached to housing 104 area number of flow components, which are provided either in part orcompletely on or in cassette 100 a. As illustrated, dialyzers 20 and 30are attached to housing 104. The tubing 102 extends so as to be able toloop around a pump head portion of blood peristaltic pump and connectsfluidly to housing 104 of cassette 100 a. The arterial and venouspatient lines 44 a and 44 b respectively also are attached to orcommunicate with cassette 100 a. As illustrated in FIG. 34, patientaccess lines 44 a and 44 b are initially connected together to preservethe sterilization of air within those lines. A number of sensors, suchas pressure sensors 46 are further integrated with cassette 100 a.

For reference, drain container 12 and solution bags 14 to 18 are shownin one possible proximal position to cassette 100 a in FIG. 34. Bags 12to 18 connect via tubes (not illustrated) to bag ports 132 to 138,respectively, extending from housing 104 of cassette 100 a. Ports 132 to138 are also shown in FIGS. 2 and 3. FIGS. 2 and 3 also show a number ofadditional ports. For example, ports 106 connect to dialyzers 20 and 30.Ports 108 connected to peristaltic pump 102 shown in FIGS. 2 and 12.FIGS. 2, 3 and 12 also show a number of additional ports 116, which areconnected to filters 20, 30 as noted in connection with FIGS. 2 and 3.Additional ports, such as ports 116, and valve portions 156 can be addedto cassette 100 a to operate and communicate with sorbent cartridge 222of FIGS. 5 to 8.

FIG. 34 also illustrates a number of the devices that are housed insidethe blood treatment machine. For example, FIG. 34 illustrates a numberof valves 56, which are operably connected to cassette valve positions156 shown in FIG. 2. The fluids at all time flow through the sterilecassette 100 a, which is disposable. The mechanics and electronics ofvalves 56, on the other hand, are placed inside the machine and reused.In a similar manner, heater 58 couples operably to fluid heating portion158 of cassette 100 a shown in FIG. 2. FIG. 34 also shows drip chambers52 (referring collectively to chambers 52 a to 52 c, e.g.) as well astemperature sensors 62 operable with cassette 100 a. Further, infusionpump actuators of pumps 22 and 24, shown in FIG. 12, are coupledoperably to pump chambers 122 and 124 as seen in FIG. 2. Likewise,ultrafiltrate pump actuators or pumps 26 and 28 are coupled operably topump chambers 126 and 128 shown in FIG. 2.

Referring now to FIG. 35, the flow devices of FIG. 34 are shown thistime housed inside blood treatment machine 150. Blood treatment machine150 is a machine that performs any of the systems and therapiesdescribed herein. FIG. 35 illustrates that in one embodiment, drain bag12 and solution bags 14 to 18 are stored in operation in a two-by-twoarrangement on top of machine 150. Machine 150 also shows the relativeplacement of cassette 100 within machine 150. In particular, bag ports132 to 138 extend upwardly from the top of the machine in relativelyclose proximity to bags 12 to 18. Ports 116 (e.g., attaching to thedialyzers or hemofilters, the sorbent cartridge or attaching dripchambers 52, etc.) extend from the side of machine 150.

FIG. 35 also illustrates that peristaltic pump blood line 102 extendsoutside machine 150 and mates with the pumping head portion of theperistaltic pump 48, which is housed mainly inside machine 150, butwhich has a rotating head that is located outside machine 150 to receivetube 102. Cassette 100 a slides almost entirely inside machine 150,leaving dialyzers 20 and 30, peristaltic line 102, patient access lines44 a and 44 b and ports 116 outside of machine 150.

Machine 150 includes a graphical user interface 160 that enables thepatient 42, nurse or other operator, to begin therapy, monitor therapy,receive status messages from the therapy, as well as collect data forpost-therapy analysis of the patient's treatment and status. Graphicaluser interface (“GUI”) 160 allows patient 42 or other operator to selectthe desired therapy and to adjust the desired or necessary fluid loss orUF volume for each treatment. GUI 160 receives prescription entries viathe packetized or checked data packets via memory card, flash memory,modem, internet connection, or other suitable local area or wide areamode of data communication. The electronic and software architecturerunning GUI 160 is redundant in one preferred embodiment, so thatmonitoring and controlling any critical function is executed throughseparate hardware and software.

GUI 160 in one embodiment includes a touch screen that enables thepatient 42 or operator to enter desired parameters. In an alternativeembodiment, GUI 160 uses electromechanical devices, membrane switches,voice activation, memory cards, or any combination of theabove-described input devices. In one embodiment, GUI 160 is run viamultiple processors, such as a supervisory/delegate processor system. Aseparate processor is provided for monitoring and checking that thecritical functions of the machine are being performed correctly. Thatis, while one processor is dedicated to controlling the flow devices ofthe system to achieve the desired therapy, another processor is providedto check that the hardware processor and the associated flow devices areoperating properly.

FIGS. 36 and 37 illustrate an alternative blood treatment machine 170,which differs from machine 150 primarily in the arrangement of drawingbag 12 and solution bags 14 to 18. In particular, machine 170 uses acarousel-type arrangement 172 that enables containers 12 to 18 to hangvertically.

FIG. 36 illustrates cassette 100 a removed from machine 170. Machine 170defines slot 174 shown in FIG. 36, which enables cassette 100 a to beinserted into machine 170, as illustrated by FIG. 37. As illustrated,machine 170 employs GUI 160 described above in connection with FIG. 35.FIGS. 35 to 37 illustrate that it is possible to configure the supportof solution bags 12 to 18 in multiple ways.

Referring now to FIGS. 38 to 41, an alternative blood treatment machine180 employs linear tubing pumps to move one or both the dialysate andblood instead of the pumps described above for such fluid transport.Indeed, it is possible to use any one of a multitude of different typesof pumping technologies for either the dialysate flow path or thepatient's blood circuit. For example, as shown in FIG. 34, peristalticpumps, such as pump 48, used earlier for the blood circuit can be usedinstead of the volumetric pumps 22 to 28 described above for thedialysate flow path. The peristaltic pumps, like pump 48, are locatedmainly in the blood therapy machine and receive tubes outside themachine, similar to tube 102, but which pump dialysate or therapy fluid.

Machine 180 of FIG. 38 illustrates a similar type of alternative, whichuses a series of adjacently placed round driver fingers 182 that rungenerally perpendicular to dialysate or therapy flow tubes, which arelocated within alternative cassette 190. Linear fingers 182 compressdialysate tubes 184 sequentially in a manner similar to the rollers in aperistaltic pump to compress and move fluid within flexible dialysatetubes 184 of cassette 100 b through such tubes and to the desireddestination for the fluid. High flux dialyzers 20 and 30 connect toalternative cassette 100 b as described above and in one embodimentextend from one side of machine 180 as illustrated. One or more motors186 are provided to rotate cams that drive linear fingers 182 accordingto the prescribed sequence.

Referring now to FIG. 39, one embodiment of the linear tubing system isillustrated. Here, drain bag 12 and a plurality of solution bags 14, 16,18 and 188 are supported by a tabletop 192. Tubing connections, such asvia tubes 194 and 196, are made between the alternative cassette 100 band the bags 12 to 18 and 188. Cassette 100 b is positioned into a slot198 defined by machine 180. Machine 180 also includes GUI 160 describedabove.

Referring now to FIGS. 40 and 41, cassette 100 b and an alternativecassette 100 c illustrate schematically and respectively variousembodiments for configuring the cassettes of the present invention tooperate with linear tubing pumps. Cassettes 100 b and 100 c both operatewith drain bag 12 and solution bags 14 to 18 and 188. Both cassettes 100b and 100 c include a number of sensors, such as blood leak detector 66,a plurality of pressure sensors 46 and a plurality of air/water levelsensors 68. Both cassettes 100 b and 100 c operate with externallymounted high flux dialyzers 20 and 30 as discussed above. A restriction40 is placed in the dialysate path between the arterial and venousdialyzers.

Cassettes 100 b and 100 c both include linear tubing portions 184 shownabove in FIG. 38. FIGS. 40 and 41 illustrate one advantage of the lineartubing pumps of the present invention, namely, that the driver fingers182 associated with machine 180 are operable with linear tubing portions184 of cassette 100 b/100 c for both the blood and dialysate flow paths,eliminating the need for having two types of pumping systems.

Cassette 100 c of FIG. 41 includes an additional linear tubing portion184 that is connected fluidly with recirculation line 220, which leadsto an activated charcoal or sorbent cartridge 222. Recirculation line220 also extends from cartridge 222 into the dialysate input and of highflux dialyzer 30. The flow of dialysate to venous dialyzer 20 and fromarterial dialyzer 30 is monitored in connection with the linear tubingpumps in one embodiment via a flow measuring device that measures flowat the input line 202 into venous dialyzer 20, which senses how muchfresh dialysate is supplied from bags 14, 16, 18 and 188. A flowmeasuring device also measures the flow leaving arterial dialyzer 30 vialine 204 that leads via the leak detector 166 to drain bag 12. FIG. 41shows a branch line 206 which selectively allows a portion of the spentdialysate or UF to be shunted via recirculation line 220 to charcoal orsorbent cartridge 222 and then back into arterial dialyzer 30.

Inductive Heater

Referring now to FIGS. 42 and 43, two embodiments for the heater 58 ofthe present invention are illustrated by heaters 58 a and 58 b,respectively. As discussed, heater 58 may be any suitable type ofmedical fluid heater such as a plate heater, infrared or other type ofradiant heater, convective heater, or any combination thereof. Heater 58a, is an inductive heater or heater with an inductive coil. Inductiveheater 58 a is configured integrally or connected fixedly to adisposable cassette, such as cassette 100. Inductive heater 58 b, on theother hand, connects to the disposable cassette 100 via a pair of tubesand is located apart from the main body of cassette 100.

As seen in FIG. 42, a portion of cassette 100 is shown. Cassette 100defines fluid flow path 76 and fluid flow path 78. In the illustratedembodiment, fluid flow path 76 is the inlet to inductive heater 58 a.Fluid flow path 78 is the outlet of fluid heater 58 a. That is, a freshdialysate pump can pump fluid to flow path 76 and into a fluid chamber74 a defined by heater housing 72 a. The heated fluid then flows fromfluid chamber 74 a through flow channel 78 for example to a dialyzer orvolumetric balancing device.

Regarding inline heater 58 b, fluid flows via a dialysate pump through atube (not illustrated) connected sealingly to inlet port 82. Fluid flowsout of heater 58 b to the disposable cassette through a tube (notillustrated) connected sealingly to outlet port 84 and a similar portlocated on the main body of the disposable cassette.

Heaters 58 a and 58 b each include a heating element or inductive coil80. Heater element 80 is inserted into each of the fluid flow channels74 a and 74 b. In an embodiment, heater element 80 is substantiallycylindrical and when placed within the substantially cylindricalhousings 72 a and 72 b, respectively, creates an annular fluid flow paththat flows longitudinally down the outside of heater element 80 and upthe inside of heater element 80 before leaving heater 58 a or 58 b.Heater elements 80 can be corrugated or otherwise have fin-likestructures to increase the surface area of the heating element withrespect to the fluid flowing through heaters 58 a and 58 b.

In an embodiment, heater element 80 is a or acts as a shorted secondarycoil of a transformer. The closed or looped element does not allowenergy to dissipate electrically, instead is converted to heat. Atransformer located in the machine includes a primary coil. The primarycoil can be powered by an AC high frequency supplier.

The fluid heaters 58 a and 58 b incorporate one or more temperaturesensors located so that the temperature of the liquid flowing throughthe heater can be monitored. The temperature sensors in one embodimentare infrared temperature sensors. Heater element 80 in an embodiment ismade of a non-corrosive metal, such as stainless steel.

In operation, cold or room temperature dialysate is pumped into theinduction heaters 58 a or 58 b along the outside of heater element 80,around the bottom of heater element 80 and then along the inside ofheater element 80, finally exiting the heater. In an embodiment, thedisposable cassette, such as cassette 100 is inserted such that theheating cavity defined by housing 72 a is as positioned directly on theprimary coil located within the renal therapy machine. When energized,the primary coil magnetically induces a current into the shorted coil80, causing the element 80 and surrounding fluid to heat. The primarycoil serves a secondary purpose of centering and steadying the cassettewithin the renal failure therapy machine.

In one implementation, the surface area of the element 80 may be aroundor less than ten square inches to heat dialysate from five degreesCelsius to thirty-seven degrees Celsius at a flow rate of approximate150 milliliters per minute. The heater may have a dimension of about 1inch (25.4 mm) in diameter by 1.5 inches (38.1 mm). Other sizes, shapesand/or multiple coils 80 may be used alternatively.

Cassette with Balance Chambers

Referring now to FIG. 44, a portion of cassette 100 shown incross-section illustrates one embodiment for providing a cassette-basedbalance chamber 340 of the present invention. Cassette 100 (includingeach of the cassettes 100 a to 100 c) includes an upper portion 96, alower portion 98 and a flexible sheeting 346. In an embodiment, portions96 and 98 are made of a suitable rigid plastic. In an embodiment,flexible membrane or diaphragm 346 is made of a suitable plastic orrubber material, such as PVC, non DEHP PVC, Krayton polypropylenemixture or similar materials.

The sheeting 346 is welded or bonded to one half 96 or 98. Excesssheeting is trimmed. The two portions 96 and 98 are then bonded at amating interface between the portions. This captures the sheeting 346between portions 96 and 98. Portions 96 and 98 are configured so thatthe welding of sheeting 346 is constrained between portions 96 and 98.Portions 96 and 98 thereby sandwich the flexible membrane or diaphragm346 of the cassette.

Using the same nomenclature from FIGS. 17 to 21 for the inlet and outletflow paths to balance chamber 340, upper portion 96, which receives anddispenses fresh dialysate, defines an inlet flow path 334 and an outletfresh fluid flow path 314. Likewise, lower portion 98, which receivesand dispenses effluent dialysate defines and inlet effluent path 336 andan outlet effluent 338. Those fluid paths are in fluid communicationwith the like numbered fluid lines shown in FIGS. 17 to 21.

When balance chamber 340 is full of fresh fluid, a valve locatedupstream of the balance chamber and fresh fluid path 334 is closed. Topush dialysate to the patient or dialyzer, a valve communicating withinlet effluent line 336 is opened as is a valve communicating with freshdialysate delivery line 314. That valve configuration enablespressurized effluent fluid to push membrane or diaphragm 346 away fromthe opening of effluent inlet 336 and towards the top of chamber 340,thereby dispelling fresh dialysate within chamber 340 to a dialyzer orpatient.

Balance chamber 340 may be oriented horizontally as shown or vertically.If vertically, the inlets are preferably located below the outlets tobetter enable air to escape from the fluid. Also, the ports may becombined to a single port for each chamber, similar to the alternativevalve configuration of FIG. 38 for the balance tube. The single portsmay be located closer to or directly adjacent to the interface betweenportions 96 or 98 as desired.

In another embodiment (not illustrated) the portion of cassette 100 thatprovides a balance chamber does not include upper and lower rigidportions 96 and 98. Instead that portion of cassette 100 includesthree-ply or three separate flexible membranes. When the cassette isloaded into the renal failure therapy machine, the machine pulls avacuum on the two outer membranes, causing the outer membranes to besucked against the machine walls defining the balance chamber. Thisconfiguration reduces the amount of rigid plastic needed and is believedto be simpler and cheaper to produce. In an alternative configuration,the pressures in the balance chamber cavities push the sheeting toconform to the cavities, negating the need for a vacuum. The outer pliesmay have ports formed integrally with or connected sealingly to theplies to mate with inlet and outlet dialysate lines.

Balance Tube

Referring now to FIG. 45, one embodiment of the balance tube 360 isillustrated. As discussed above and using like nomenclature, balancetube 360 includes a separator 366, which functions similar to theflexible membrane 346 of balance chamber 340. In the illustratedembodiment, separator 366 is a ball or spherical object that movessnuggly within a cylindrical housing 382. A pair of caps 384 and 386 areprovided on either end of cylindrical housing 382. Caps 384 and 386 sealto cylindrical tubing 382 via outer O-rings 388. Separator or ball 366seals to caps 384 and 386 via inner O-rings 392. In an alternativeembodiment, caps 384 and 386 are permanently or hermetically sealed tocylindrical tube 382. Ports 394 and 396 are formed integrally with orare attached to caps 384 and 386, respectively. Ports 394 and 396 sealto mating tubes via any mechanism known to those with skill in the art.

In an embodiment, cylindrical tube 382 is translucent or transparent, sothat an optical sensor can detect if ball or separator 366 has properlyreached the end of travel. Ultrasonic or other types of sensors may beused alternatively. The assembly could be made of two pieces ofinjection molded plastic that mate in the center of the tubes with theseparator 366 installed prior to mating. Mating may be done by solventbond, ultrasound or other techniques known to one of skill in the art.Tube 382 may also be a simple extrusion with molded end caps applied bya secondary operation.

Ball or separator 366 is sized to fit snuggly but smoothly within theinterior of cylinder 382. A small amount of mixing between fresh andeffluent fluid may occur without substantially affecting the performanceof the system. In an alternative embodiment, a cylindrical piston typeseparator is provided. In either case, separator 366 may have additionalsealing apparatus, such as wipers or deformable flanges that help toenhance the sliding or rolling seal as the case may be.

Each of the components shown in FIG. 45 for balance tube 360 may be madeof plastic or other suitable material. In an embodiment, balance tube360 is a disposable item, which may be formed integrally with cassette100 or attached to the cassette via tubing, similar to heaters 58 a and58 b of FIGS. 42 and 43. It is important to note that the O-rings andfittings are not be necessary if injection molded caps or assemblies areused. In addition, sensors such as ultrasonic or optical sensors, forthe positioning of the separator can eliminate a need for sealing at theend of the tube.

It should be understood that various changes and modifications to thepresently preferred embodiments described herein will be apparent tothose skilled in the art. Such changes and modifications can be madewithout departing from the spirit and scope of the present invention andwithout diminishing its intended advantages. It is therefore intendedthat such changes and modifications be covered by the appended claims.

1. A medical fluid therapy system comprising: a blood line configuredand arranged to be coupled to a patient; a blood pump connected to theblood line; a blood filter in communication with the blood line, thefilter operable to allow a liquid portion of a patient's blood to passfrom the filter to a therapy fluid flow path; a pair of peristalticfluid pumps positioned and arranged to pump therapy fluid to one of theblood filter and the blood line and from the blood filter; and at leastone balance tube, including a tube and a separator mechanically freefrom first and second fluidly sealed closed ends of the balance tube,the separator fitted tightly and moveably back and forth betweenend-of-stroke positions within the tube for volumetric control thatassumes a constant volume is maintained collectively between (i) thefirst closed end and the separator and (ii) the separator and the secondclosed end, regardless of an orientation of the balance tube, ortortuous path volume control device, the balance tube or tortuous pathvolume control device in fluid communication with the pair ofperistaltic pumps and operable to control an amount of therapy fluidthat is pumped to the blood filter or the blood line and an amount ofthe fluid that is pumped from the filter.
 2. The medical fluid therapysystem of claim 1, which includes a plurality of valves operable tocontrol the balance tube or tortuous path volume control device.
 3. Themedical fluid therapy system of claim 1, which is programmed toselectively pump therapy fluid to the blood line upstream or downstreamof the filter.
 4. The medical fluid therapy system of claim 1, which isconfigured to pump therapy fluid to the filter to perform convectiveblood clearance, diffusive blood clearance or a combination thereof. 5.The medical fluid therapy system of claim 1, wherein the at least onebalance tube or tortuous path volume control device is further operableto control an amount of ultrafiltrate pumped from the filter.
 6. Themedical fluid therapy system of claim 1, which includes a pair of one ofthe balance tubes and the tortuous paths, the pair configured to operatesuch that one of the pair pumps to the filter/blood line while the otherof the pair pumps from the filter.
 7. The medical fluid therapy systemof claim 1, wherein the volume control device is part of a disposablecassette positioned and arranged to operate with the pair of peristalticpumps.
 8. A dialysis system comprising: a dialysis instrument includingfirst and second dialysate pump actuators; and a disposable cassetteoperable with the dialysis instrument, the disposable cassette includingfirst and second portions configured to operate respectively with thefirst and second dialysate pump actuators, the disposable cassettefurther including at least one balance tube configured to meter anamount of fresh dialysate delivered to and an amount of spent dialysateremoved from a patient, the balance tube defining a longitudinal axisand including a separator within the tube, the separator mechanicallyfree from first and second fluidly sealed closed ends of the balancetube and to move back and forth along the longitudinal axis within thetube to meter the dialysate to and from the patient.
 9. The dialysissystem of claim 8, wherein the at least one balance tube is furtherconfigured to meter an amount of ultrafiltrate removed from the patient.10. The dialysis system of claim 8, which is a blood treatment dialysissystem, and wherein the at least one balance tube is configured to meterthe amount of spent fluid removed from the patient through a bloodfilter.
 11. The dialysis system of claim 8, including first and secondbalance tubes, the first and second pump portions of the disposablecassette located upstream of the first and second balance tubes.
 12. Thedialysis system of claim 11, the first pump portion valved toalternating drive fresh dialysate to a fresh dialysate inlet of thefirst balance tube and the second balance tube, the second pump portionvalved to alternatingly drive spent dialysate to a spent dialysate inletof the first balance tube and the second balance tube.
 13. The dialysissystem of claim 11, the first and second balance tubes each including afresh fluid outlet in fluid communication with the patient and a spentfluid outlet in fluid communication with a drain.
 14. The dialysissystem of claim 8, including first and second balance tubes each havinga fresh dialysate outlet leading to a common fresh dialysate line, theline valved such that fresh dialysate from the fresh dialysate outlet ofthe first balance tube can be directed to the fresh dialysate outlet ofthe second balance tube to meter an amount of ultrafiltration from thesecond balance tube.
 15. The dialysis system of claim 8, which includesat least one sensor positioned to sense an end of travel of theseparator within the at least one balance tube.
 16. The dialysis systemof claim 8, wherein the separator is at least substantially spherical.17. The dialysis system of claim 8, including first and second teesconnected to first and second ends of the at least one balance tube,each tee further connected to a fresh dialysate line and a spentdialysate line.